Date : Tim : Place :

NOTES PREPARt..ll BY DR, B\KER

FOR THE

EIGHTH ANNUAL INDIANA PATHOLOGY SEHINAR

FUNGOUS INFECTIONS AND OTHEft I NFECTIOUS GRANULO~S

!1ay 20, 1956

PRESENTED a: :

Roger D. Baker , H. D. Professor of Pathology

Duke University School of l'.edicine

Chi ef, Labora t ory Service Ve t er ans Administrati on Hospital

Durham, North Carolina

Sponsored jointly h'J :

/<::70

10:00 A, M. (C,D, T. ) Vet erans Adm. Hospital l h81 ~lest l Ot h Street Ihdi anapolis , Indiana

Indiana Ass •n. of Fatholoeists Indiana CancE:r Society U. S. Vete rans ;\(jm, Hosoital. Ind i ana Univ. School o{ Hedicine

DL'!GNOSES

1, Bl.astoi!\Yc osis • 17TH "~·~l.'•C" ") ff lu..,(· ·Wl> fll'.,STJ:\R.. -

2, Histoplasmosis .,,..v"" ~>CII.>C

}, Hue Ort11)7Cosis t f p.;_,,~ , , ._ s..:'F>•) 1:. Sporotrichosis " lot' I~ \. .. o 0 bM'I ...... ., -ov

S. Blastoi11)Tcosis • D'I\1 """~t>.t(t> .. ,) OY $l<:i,.J

6. cat-Scratch Diseas e or L"M \1 I . E. I •f \..

1. Hard Tubercle s of Spleen and Liver Suggestive of Boock 's Sarcoid, "Hyp(;rsplenism. " Ques tion of Blood Dyscrasia , ku , gf'..;: ,

8, Lettcrer..Siwo •s Disease u ::.

9. Leprosy of . .._ ~

10, Leishmaniasis , ~ W• tl

llo B<lr yllosis D~ IC.I t.l

12 , Crypt oc oc c osis of LVIJV

13. Actinai11)TCDSis c p hi ..JIJ f2-

lL. Tularemia • ~\(0 Li" t:.R. ~r _e " 1'\N ,!:> L'1ft!P!-! ~JDW I

15. Cr;ptococcosis L en \

16. South American Blastai11)TC osis ){=- Cl<tl

17. Sough 1\m'lrican Blas tOI!\YC osis f 1,;{.,

18. CoccidioidOI!\YCOsis

19. Hucormyc 05is ... ~(:,

20, Nocardiosis ~

21, candidiasis ~

22 0 Cryptococcosis • ,cJIJ ~

{0 D

}

2

DISCUSSION

Case 1. The duration of the clinical course of the disease was 5 months.

kt autopsy ther e were l esions in lungs, pl eurae , hilar nodes and prosta t e .

In the mi c r oscopic section of l ung there is suppurative pneumonia ; F~~­

gus cells 12 micra in diameter are t o be seen, toget her with giant cells <tnd

caseous necrosis. In the prostat e a necrotic a r ea is bordered by giant cells

which contain double.ccntoured budding fungus cells.

A Gridley stain (Peri odic Acid-Schiff and Gomorils Aldeeyde-Fuchsin St:tin)

demonstrates how numerous the organisms are, and how t hey bud, but it dces not

sho~l t he dcuble coo t our . Since t he background has .a neutral uniform tonc,

the Gridley stain is unexcell ed for demonstrating t he p resence of fungi in

tissues. It is useful i n sear.;: hirig for fungi in tissues when the presence

or absence of fungi in microscopic sections is to be established.

For the technique of the Gridley stain consult Conant, ~mith, Baker,

Callo~my and Hartin, 11 Hanual of Clinical ttrcol ogy, " Second Edition, ~'~ . B.

Saunders Compaey, Philadelphi a , 1954, P• 421, or Gridley, l'l. F. A Stain for

Fun~i in Tissue Sections . Am. J . Clin. Path., 23:30.3, 1953. The PAS (periodic

acid-·Schiff) and t he l!l3thenamine silver stain are also excellent to demonstra t e

blo.ston-1fcet es in tissu-3. (See the discussion of Case .3 f er the 100thod of tho

silver stain.)

\vhile the diagnosis i s secure on hi st ol ogical gr ounds, it is desirable

t o make the diagnosis from the sputum, pleura l fluid or prstatic secretion,

in we t , unstained pre par at i ons.

it is a highl y desirabl e step.

Cul ture is not necessary f or diagnosis t hough

Skin testing with blastcll\Ycir. gives a reaction

of the tuberculin type, though it may be negative in severe cases. Comple ment

fixa t i on tests may be positive or negative .

.3

Clinical diagnosis is important because treatment ~lith hydroxystilbamidino

is ef.t:ective.

Diagnosis: Systemic Ncrth American Bl.astoll\YCOsis.

Case 2. Tho lymph node i "S densely infiltrated t~ith rnacrophages containing

br.sophilic dots separated by a space f rom an oval capsule or circle . 'l'he

capsule of the organism is Hell damonstra t ed in the PAS stain.

The clinical story is charac teristic of gane.ralized histoplasmosis in an

i nfant with involvement cf the .reticuloendothelial system, tha t is, sple,m, l i ver,

lymph nodes and w..rrcw. Tho bone marro~1 i nvcl vemont is r esponsible f er tho

l eukopeni a .

Presumably the infant had inhaled fungus-containing naterial and a pulmcn-

ary focus had led t o systemic involvelll3nt.

\ve hav0 tho additional information in this case that the mancw •.-~hich t~as

asp.i ratad three days after admission, because of the possibilit y of histc:plas-

mosis , presented numerous or ganisms ·engulfed i n macrophages .

The d i agnosis is reasonably secure without cult-ure , The tr<3atment Hith

e t hyl vanillat o and whole bl ood transfusions appear ed to be of l ittle value in

the case;.

For culture, flasks · of brain-heart infusion glucose broth (100· ml.)

shoul d be inoculated ~li th 2 to 5 ml. of blood or sternal marrow for incubation

at 370C. Tissue from aut opsy spec imens should be incculated on brain- haErt

infusion glucose bloo:l agar slants for incubation at 37oc. and on Sabcuraud •s

gl ucose agar slants for inouba t i cm at I'ocm t e mpe r ature , A :thoroughly secure

diagnosis is based on cultures which demonstrate the typical colony and tuber-

culate spore s char acteristic of H. oapsulatum.

Diaenosis : Progressive Histopl asmosis .

'

4

Cas<l 3. A diabetic died eleven days af ter an episode cf diabetic cci!losis and

chill. There had been proptosis and facial parolysis. The r i ght carotid artor.r

was ·~hrombosed and there wera areas of s oftening of t he ce r ebrum.

This clinical - stc·ry and gr oss pathological findings are practic:~lly

pathognomonic of cerebral mucorrzycosis and have b6en r epeatedl y cbserv<Od in

fa tal cases. Two cases havo boon observed in which !Jiagnosis bas beon nndo

clinically an:i tho progress of tht: mycosis has been oolted b'y rigorous C('ntrcl

of tho diabetes .

Qur slide present s meningcvascular nercosis and nercot ic enc.,phalitis . The

softcnint; of the brain represents infarction due t o vascular tlu·cmbcsis, The

m2ningeal vessels are infiltrated with ncn- sept:lte hyphae cf 10 to 20 nicra

in thickness, The methenamine silver stair, is excellent f or demonotrctinh the

fungus in tissues .

In three cases of the cerebral f or m of mucornerc osis in ~lhich cultures have

been successful the fungus has been of the genus Rhizopus .

Tho disease has occurred most freqll(;ntly in acidotic diabetics, out alsc

in othor predisposing conditions ~nd even in persons without knc•m predisposing

con,!itions.

'rhero is no known fungicidal drug which can be recommended .

Diaenosis during life has been ma1e by tissue oxami~V>ticn ci' an ulcer cf

the hard palate, of sinus mucous menbrane t!nd of tissue frcm the brain, No

:!i.ar,nosis bas been made by examinatic-n cf spin::l fluid C'r exttdates so fo.r <\s

I know.

;

. J ,·,

•

5

Technic fC>r methenamine silver stain:

'!'hose results were obtained by the use of a combination of "Tho (!r~ • .• _ .

Eurtnor ~thenamine Silver H:~thod for hrgontaffin Cells, " (Stain Technnl , 24:225,

1949) and • the J.lethenamine Silver rlethod," Gomori, (Am. J , Clin, Path,, Toch,

Sect, 10:177, 1946) as f cund in Histcpatholoeic Technic and Practic~l Histo­

chondstzy, Lillie, R, D,, 1954.

Solutions :

Stock methenamine silver solution: Dissolve J gm, methenamine (hexamothyletw tetr ami no) in 100 ml , of distilled water, Add 5 cc , of 5~ aqueous silver nitrate , (This soluticn keeps for months in a cold, dark place) .

'.forking Solution: Stock I!Cthcnamine silver solution Holmes 1 borate buffer (pH 7, 6)

Holmes 1 Bora to Buffer : (a) Boric acid (AR)

Distilled water

{b) Borax Distilled water

pH 7.8 -- (a) 16 ml, plus {b) 4 ml,

30 ml, 6 rnl,

12, 4 gm, ) 1,ooo ml , )

19 ,0 bm, ) 1,000 rnl , )

Fixation: ite used !erwin or Helly- fi.xed tissue,

Qlo.sswaro : Should be chemical ly clean, rinsed woll with iron- free dist illed Hater, and previous silver deposits removed Hith concentr ated nitric acid,

Technic :

1 , B~_ng sections to water as usual , de:oenkerizin£ if necessary, 2 , Place in S% chromic acid for 1 hour. J , \~ash in running water f or 5 minutes , 4, Rinse in distilled water, 2 changes , 5. Place sections in Coplin jars contcining tho buffered mathenamine

silver scluticn which has beon preheated to 60°0, Hopl;1ce in oven at 600C. f or 1 - 1 1/2 hours , (A.t'tor about 1 hour rir1S0 a slide in d i stilled water ancl check with microscope , r epeatinrr a t ab, ut 15 minute intervals until fun:;us becci1Xls pr o!l'.:inOnt . It shoulU be. a definite but transparent br own on a usually ~lle t o 00larless back­ground nt this point. )

6 , Rinse in distilled water. 7 , Tcne in O, l l( cold chloride for 10 minutes ,

6

6 , Rinse in distilled water , 9 . Fix in 5% aqueous thiosulfate for 2 minutes ,

10, Hash in runnine w;atcr for 5 minutes, 11, Counterstain in 0 . 5% safranih 0 in 0. 1% acetic acid f or 5 minut es , 12, DeeydratG in acet one, clear in xylene, mount in permount or b,Hs:!m,

Rosults : Fungus black, backgroun:i oright red. ( !. fow ether tissue c.lements lrilY show the silver, <!oponding

upon thc t ornp<::raturo :m1 l~ngth or staini.ng tine , )

Dia1jncsis: Cerebral !1ucorrwcos1s,

Cnoo 4. our section is frcm an ulcer of 6 mcnthe • durati cn frr m the ar:n of a

f~.rtn t.cy. Of cutaneous lll'fCoses :,no thil'~l<s of sporotrichosis, l:.lastm~·ccsis,

an:i chromotlastoll\'{cosis. Sor es up the arm are chaructvristic of sporot richosis ,

The ~urntion is l onP, for tulremia,

Your secticn presents chronic dermati tis with ciant collz. Spacial F~S

stAin shoHS no fungi in .:;i ant cells nor arc fund rlemonstr:J. t ed in the Gri<'.l ey

sta in, This rule s out chr~moblastcrnwcosis and blast cll\'{cosis in wbioh tho £unci

arE: rea".!il;r demonstra ted in giant c to lls,

The histclc~,; ic dia€Jlosis is chrcnic dC;rm::.titis -w'i.th ,:;i.lnt cells, ~lith a

pr~,Jsumption in favor of sp cr otrichosis because oi the clinical fonturos and the

lack (If demonstrable or eanisrn.s in tissue secticn, .

I am happy t c say tl>at cultures frCIIll tho l esion were positive for

Spr.rotrichum schenckii,

In most casr;s, as in this ono , the di aJ nosis cf sp0r ctriahosi:; mus t to

m·1de by culture . " fatal h=n !~enorali~<:d caso in Cincin."lati shC'l-rod nwriais of

cr ranisms in th& l esi <ns, like the l c sicns cf experillEntally inocul2.tc:! mice ,

AEf!lutinations , skin t ests and complement fixation t ests rr.:ly be dc·ne t o

supplement cultural ll¥:lthorts ,

Potassium i cdido ccntinucs t o bo the specific in the trcatmont of

7

sporotr ichosis .

Ili~.gnosis: Sporotri chos i s of skin,

Case 5. Like t he previous case this was a chronic ulcerating skin l es ion cf

six nwnt hs 1 durat ion, Of lliYCOses, one would think of the Mm;;; three, per na:::Js

t,,i th thu addition cf cutaneous h i s t opl asmosi s,

our s l idg pr e sents chronic dermatitis with microabscesses, Gi a nt cells

anr.\ gr eat <r:p iderma.l hype.rtropey, Budding doublc. contoured yeast f orms are

f oun:l in giant cells and in the microacscesscs, A Gridley stain sh'' '{S that the

cr t;an;.sms are numerous, but not nearly as nUlllEirous as in systemic blastc.nwccsis,

Cutaneous blastolliYcosis is cl>:ronic, but i t ~ce s n()t tend t.o l ene r alize and

l <:acl to death ?.s dces systemic blastV11ifCOSis ,

The diat:n ,.s i s is r cas cnnbly secure fr om t issue oxamimti(ll1 , Direct mois t

' preparations t<ill al so provide a diagnosis ,

The treatrr~nt is t he sare as f or systemic blastolliYc osis, Stilbami·::ine

~Y be ::lpf?lied l ocally and x- ray nay l:;e G·iven lccallr ,

Dia:;-ncsis : Cuta.necus North A.re rican Blasto!Tij'cosis ,

Case 6, A mass in the l e ft axilla , n0tod 9 ~.ays previ.:usly, was oxci socl ,

Slides from 2 diffe r ent bl ccl<S 1~ere distri0uted, In one tho.ro is a lymph

node ~lith in.fbnation and fibrosis ~mar by, In t he other only the inflzromation

and fibr osis ar e pr esent , Tho pr ecess is l argely perincdal.

The slide ~rith t he node sho"'s an oncapsula t od nccrctic f ocus extending in t o

the node, In porinodal fat ther e a r c f oci of necrcsis Hi.th surr ounding fi1-roblasts

or epithelioi d cells, SolllO t'f the precess is dd enough t o c~ ccll~gent•us , In

the other slide tho process is tho same, --r egi ons of oocros i s wi th surrcunc'.ill(!

macropha,:;ic t•r fib r oblastic tissue . GU.nt cells aro not s~on.

8

:Jis tol ogically tho appearance s s uggest tho s am:; a s the clini ca l circUinstances

d o, ca t - scratch di sease , Wi thout 3 c nt s to conte nd ,.,j.t h ¥10 liioul<;l have thGU,~:1t of

;:, 'V:.\ri~ty of condi t ions ~Ibich produce caseous losicns, sccb as tularemi a ,

l jr.rophopathia vene r e um, sporotri c hosi s , t ubc::rculos i s , plaeue or even pyoE:e nic

precesses l ike c occa l or bacillary i nfections , Stains f or a c id- f-ast !:,:,ci:Ui,

e;ram-pos i tive and gran~negatiw bacteri a, and f unc;i have al l been ne ga tive fOl'

vrranisms.

on this basis I ,,;culd net favor t ube r culosis or pyogeniq i n fect i on "r plague

Le cause the necrosis is recent and one vioulil therefore e::-:;:>ect t o be a'.:ll0 t (l

demonstr u. t e crganisms, Cat- scr a tch fe ver , l ymphopath ia, tularemia and spor(·trichc~

sis 'tloUld appear t o be mor e l ikel y , The cl i nical f ea turcs arc: not su;J,;<-sti ve of

spor otri chc-sis;' lymphopat P.ia is unusual in this l ocation; and there were ca ts,

We luw.e the adeli t i e>rml infc-r m-"ti on in thibs case thr.ct afte r bi ops-,t i t tvns

learno<:! that t he patient had had se;vural Sin<tll scratches , A sug"esticn t o have

tho ant i ge n te s t f or cat - scrat c h disO~!SG per f crrnd. wa s net .fc·llc,.,Gd Ly tho

nttc nr.lin:;: ·physi c i an.

Di ncmosis: Necrotizinr-' and Fi:...r osinr; Fer ilylT".flhadenitis of J..xilln Consistent Nith

cct- Scl'atch Disease ,

Case 7, Splom' me{;aly and hepatomegal y He re pr.cminent f oatu1·es cf this ''l<: l'llD.n t s

ill nes s, She had l e ukopenia and gr anulccytope ni e , FcllcNing Sjillenectomy the

pat i e nt's symptoms d is.appear ed t ut t oo ;Ihite c e>unt Na·s a bnormally hi;~h , The

course susges t s that t here had been "hype·rsplenism" a:nd that removal ci' th·~

spl oon was .bene f i c i al, Does t he pat i ent ha ve l e u.l<e mi.a 8 mont hs aft er t he oper a t ion'

9

Our slide of spleen presents macrophagic tubercl es in the spl enic nodules ,

The macr.ophages of these hard tubercles contain vacuoles, Other hard tube1·cles

contain giant cells, Throuzhout thEl pulp there is i nc rca.se i n white celJ.s ,

Clusters of pl asma cells nnd of large nucleated cells occur in the pulp,

The~ were smaller tubercles in the l iver ,

Special stains for acid fast and pyoeenic bacteria and for fungi fail to

she;/ any or ganisms in the tubercles ,

The hor d tubercl es in spleen and l iver ar c s ugge stive of Be-eck's sarcoid, but

u0 need additional information for a d i ar::nosis, 'fhc cccurrcnce of vacu;::les in the

spl eni c lymphoi d, nodules sucrgests fat , and the l)<'Ssibil:j.ty i s suo;gestcd tb::-. t tha

tu1:-ercl es represent reaction to fat,

Do wo have a follotv• up i n this case?

Diagnosis : Har<l Tub<:rolEJs of Spl een :md Liuer Suggestive of Reeck's Sarcoid,

"Hyparspl cnism" , Question of Blood !Jysc.rasi a,

Case 6, The child died at 5 months of age having had a r ash, enlar ged l i v<:<r,

spleon, and lynph ncdes, . and radiducent defects of the sl<ull,

of fun;..'Us d i seases, histvplasmosis is suggeste::d l:r,y the onlarge~nt of the

reticuloendothelial system, l!an<l-Schuller-Ohristian 'S· di sease by the defects in

the skull, and the Lettorer-Si1~e t s disease by the r ash an~! other features ,

our lymph node .is r epl aced i:;y macrophaees as in Case 2 of this Seminer Hith

scattered feci ·or lymphoid tissue rernainine;. 'file macrc.phnees are l a r &X} ~rith very

fiM ly vacuolated abundant cytoplasm, l·!itoses are present ,

10

SiJnilar cells in th~ slightly fatty liver represent proliferation of ~upffor

cells.

Th<::re are no fungi in these cells, an observation which rules cut his­

t opl;J.sJncsis; and ·no l a r go vacuoles and fibrosis, features '..thich should be

pr esent in Hand-Schullc r - Christian Is 4i13case or gon'1lralized xanthcmatos:!.s . In fat

stains of generalized xanthoma',;osis the macr cphages a!:.sorb Sudan dyes, while

thGy usually do not in Letterer-Siwe 1 s disease, hence the synonym ncn- lipoid

r e ticulcendotheliosis . In Gaucher 1 s d i sease t ho .macrcphagcs ha~ c:~t c.'Plasmic

st1·iations. L'l Ni vmann- Picic Is di sease t h0 lllOICro,pha t;es are sudanophilic.

Diagnosis: Lotterer-Sit~e 1 s Disease.

Case 9. Residenc!lc in Louisiana, follcwcd by annular maculopapular skin l esi c::JS,

t hickeni ng of the skin and cnlar;,;em;;i:t of the nose indicates leprOS'.f• Iva should

like to kncm tha t the skin lesions Nere rievd1 of sensation Hhen stimulat"'d t;y

pin ?rick.

our b i opsy pr esents pale ncdules of macro;JhaGeS throuehout the dermj.s

an:l. ar cund capillaries and sweet 3land.s . The macroph!l{;es lacik empty or

vacuoL(Itcd , They contain laree numbers of acid-fast eaci lli., as de monstrat ed

in the Fit.c- Faraco Oil Fuchsin l"JGthcd ( see Lillie Is "HistO'patholo~; ic •rochni c and

Pr,~ctic:al Histochemistry," Bl.akiston Co,, Ne1~ York, 1954, p. 381. )

Diagnosis : Cutanc ous Lop rosy •

ll

Case 10. Two skin lesions of unknown duration were !Jrosent in a 13-y e.ar oL!

boJ f 1·om t lw f1iddl c Bast ,

In your section there is intf:lnso chronic der mat itis t~ithout the a~scess<.:s

or epi dermal lzy'[J')r pl as i a we sa~r in cutan0ous blastomycosis , The ro aro a f a ti

giant cells ,

Under oil immersion numerous or ganisms are seen >lithin t he cytoplasm of

macropha17:es, These Ol'ganisms resembl e Histopl asma capsula t um, but. are smnlle t·

and t he r e are no capsules , It wculd Mquira smears t o demons t rate mor:a of t ho

structure of Leishmania trcpica ,

Diagnosis : Cutan-eous Le ishlllaniasis.

Oriental Sore ,

Case ll. .4 lesion 1~as excised 16 months aft er <~n injury by a fluorescent light

tulJe , T!l.is his t ory is all t hat i s needed t o sug!]est the diagnosis · of

beryllium gr anuloma, .

Your section presents t ub<J rcles i n the dermis ;rith gi ant coils and

hy.-.li ne centr a l are<:s, The tuber cles consist of vacuola t ed macrcphages Suf;e;esting

those of l epr osy, No foreiGn bodi es are visualized and birefringency i s not

rlemcnstra t e rl in ;>clarized l i ght ,

Diagnos.is : ~ryllium Granuloma of Skin

Case 12, A thwub-sized nodule with a central liquid- conta ining cavity tvas

removed from t he l unr:; .

Your secticn presents case ous necr bsis t owar d the center of the ncdule a n:!

a fibr obl astic mesh~orork containing ncic rophages and giant cells further cut ,

These phagocyte s present vacuol es, s ome of ;,'hich a r o orr:,anisms, In a few in­

stance s the amount of space arcund t he centrol pa rt of tho or ganism is c onsiderable,

suv,gesting gelatin0us capsules of Crypt ococcus neof ormans, S ome of the or canisms

stai n vri t h mucicarmine stain, which is characteristic of Cryptcccccus,

12

Comparison between this case and Case 2 (histcplasmosis) on the one h:?.n-!,

and Case 22 (cryptccccccsi) on tho other, indicate a greater similarity to

cryptococcosi s on t he basis of larger size and lack of the narrow capslue 0f

Histopl asm'l .

Case 2, of histoplasmosis, shows ~roll-defined dots , Under oil illiJrersic,n,

ona can see that an eccentric part of the dot is darker and that there is :;.

capsule c l ose to the tlot ,

Diar;nosis : Cryptocccc osis of' the Lung,

Cnso 13. A disease of apparently 7 months du1·ation i n a middlG- a E,ed m.ln; cough,

pulmonary disease and fluid in the pleural cavities; congestive heart failura ,

Your section presents abscesses in lung and liver , In the abscesses are

granules composed of very narrow gram-positive uranchine filanxmts thu width of

tubercl e bacilli,

Diacnosis : Actinonvcosis, of Lunr~ and Liver.

case 14, An elderly man died three weeks after he had killed and skinned

ra';;tits . He ha<i <~n ulcer on the back of his loft hand,

Yoor slide bear s the pieces of four involved organs , In the lung thore

is necrotizing pneumonia. Mediastinal nodes and aploe n had necrotic .f'cci

which probably resembled caseous tubercles er cssly , Similar necr oses affected

tho liver, These necroses present many po:J¥morphonuclear neutrcphils with frag­

ments of neuclei .

Special s tains for acid- fast l:acilli, ordinary ba cteria c.nd funr,i a re all

negative , Since or ganisms can not be stained in sections ot human lesions of

tul:lremia, tho failure to demonstrate crganisms stronc~Y suptJcrts thr. diagnosis

of tular emia of the l ungs with hematogenous d iSS(lmination. The ulcor of the

hand was prosumatly the primary losion of tularemia , .Agglutinins should a!lpcar

in the bloQ.l 10 t o 14 days nfter infection, The nogative agglutination test 11

13

days afte r infection is d ii'ficult to expl a i n .

Diagnosis: Tult~remia with Hematogenous Disseminati on.

CastJ 15. Cer olJr a l symptoms for f our months, with bila t er a l dilata t i cn of. '.>he

lat-ar a l ventricles l)f the train, were pr esent i n a middl €-a g<:d llk'ln.

our slide, of ma t erial f r om the poste r ior fossa obtained tho day bdorc

~eath, sho1.;s choroid pl exus, rsiant cel ls and neutr ophilic e':udat0 . Cryi)t ()ccccus

ni::of .orrnans is present and sh( II-IS t h i ck gel atinous capsule s . " mucicarmim: stain

dernonstrate.s budding.

we have the addi t i onal i nformati on that Cry~1tCeoccus ·neofor rnans ~~rev;

frcm th;.; ' s pina l flui d t aken at lumbar puncture , and from r crti c-ns of l ung,

pl eura and t rai n t aken at autcpS'.f .

Diagnosis: Corebrnl and Pulmonary Cryptoc c.ccosis, ('r C'rulosis) .

Case 16. A turkey eg.:;- sized cerebrp.l mass from a Brazilian contained a central

visci·C: t.rhitG nn t crial .

The external viabl e fit r r-\.!s capsul e contai ns microal:;scesscs an:! (~iant

cells . A f or m in t\w PAS ·sJ,a;i,.n ~loows ) 'bur.\s . The Grid l ey stain shv.~s 1mlltiple

blliidinr .

DiaBncsis: South American Blasto~Jcosis.

case 1.7. A farmer in Brazil d i ed aft0r a febrile c curse of m0re t han 6 ~1eoks .

At aut cp,sy there were five nodules in the lungs, an:i l a r;,e masses in t b.,; adrenal

rcs i ons • .

'rhe slide shc;1,rs a fi:,r ous ca fJSule about necrt,tic material.. In t !·,e capsule

ther e a r o r i ant cells containina c-r ganisms Hith s~rt' rims. f.lulti pl e bu:kling

i s not easily demcnstrabl 0 in hematox-.fl in and eosin. I>iultipl 8 l..uddins is lvell

seen in silve r st;oin. 1t i s gocd in the Bauer and Gridl ey stains al so.

Dia .;nosis : South hmerican Bla stonvcosis.

14

Ca.se 18, Tul:Grcla s in the lung contain r ounded or ganisms in giant cells without

aey central mass such as ens expects in t lastonvcosis . Internal materi a l is

cont inuous wi th this capsule., This is the appearance cf the deve l oping f orms

of Coccidioi des immitis,

No endosporulating f onns Here f ound in t issues . Some of t he pus from

the cervical sinUE grm~ out Coccid i oi des immitis in pultur!'l and inoculat ed

mice presented ::>11 fol'ms of the organism ;rhen killed at t he end cf a Heek,

Diagnosi s·: Cocci ;:li ci dOJeycosis of Lungs and Paravertebral Sinus,

Case 19 , The non- septate hyphae are, well seen in the slide staine<i 1~ith hemat oxyli1

and eosin, Th~lY g rc•,1 in the walls of t.lflod vessels an:l have s t i rm!lat ed t !trcmtosis,

The mut henamino silver stain demonstrates tre c rganism ,.Tell.

This i s an instance of mucornvcos i s of tho lun;:(s in a patient with leukemia ,

Refonmce : Baker, R, D. Pulmonar.r Nucornwc·osis, Amm'ic:an Journal of Pat holory 32, 267 1 (~larch-April) 19 56,

DiaGnosis : Pulmonary Mucor~crsis ,

Case 20 , The necrotizi ng pneumonia is r ich i.n noutr ophils, In gram stain

1:-r anchin;:; gram-pcsitive fila100nts are se .:ln,

Di<l"".,nosis: Nccarcliosis of Lung,

Case 21, A pati ent with chronic leukemi a , treat ed with anti-leukemic dru~,s and

anti b i ot i cs, presented ulcerations of t he di gestive tract at aut opsy.

In microscopic section the esophagus is f ound t o ce ulcer ate<i and chroni cally

inflalllBd, Cc.llo·ctions of :fungi are seen on t he surface and in deep Ulcer s , 'r.he

:(un~s, in bacteria l st-l in, is a budding yeast, 1-1ith s mall numbers of acccmp:aeying

h.)'"phae . Slll9.111 gr a m-positive bacilli are also ?r esent in small numbers .

Diat;nosis : Candi diasis cf ~sophagus.

15

Qase 22·, A lesion of the l ung was discov.ered on r out.ine x-ray of the che st and

"•as r emoved surgi cally , Gi ant cells are numerous in secti ons of tho l esi ons,

and c rntain larf,-e num\:e r s of organisms, Rar e ly these cr ganisms presE;nt t j0

flul atinous capsul ar mate rial of crypt acoccosis, The buddin;; is 1.Cll -iomonstrated

in silver st.a ins •

Culture 1~as obtained , on artificial media gelatinous capsule s were not

see n a!Jout the \Jud(ling or !.';ani sms, Tho crgains m gr~:m well at 37°C, i ndicatin;J

t hat it Has a pa t hogenic Cryptococcus, Sus;:.ensions cf the culture 1.cre. inoculat ed

into mice , In the l esions so pr o<luccd the organisms e xhibited gelatinous

capsules ami stained well '~ith muc i car mi ne ,

Diae nos i s : Cr.tptcc occos i s of Lung ,

Date : Ti me : Place :

EIGHT"! ANNUAL INDIANA PATHOLOGY SEl1INAR

FUNGCUS JNFECTIOUS AND OTHER I!IFJ!:CTIOUS GRANULOHAS

PRESENTED B{ :

Roger D. Baker, 11. D. Professor of Pathology

Duke University School oi Medicine

Chief, Laboratory Service Veterans Administration Hospital

Durham, North Carolina

Hay 20, 1956 10 :00 A. H. (C.D.T . )

Veberans Adm. Hospi t al 1.481 \-lest l Oth Street Indianapolis, Indiana

Sponsor~d j ointly ~: Indiana Ass •n. of patholoaists Indiana Cancer Soci ety u. S. Veterans Adm. Hospital Indiana Univ , School of Medicine

Case 1 , A6617

Submitted b;y: Department of Pathology Indiana Univ, School of ~~dicine

This 50 year old white man beca~~ ill in September, 1952, 5 months antemortem, with an uppur rvspiratol"'J infection complicc:ted by weakness and headaches . A cough develo!XJd Hhich :>ubs~quently was productivo of whitish and blood-streaked sputum. H;; developed pain on coughir.g and breathing, In December ho entered anotner hospital because he wo.s unablE to urinate, A diagnosis of abscess of tho lei·t kidney W:\S mlde and he was told ho had a largo prostate . He ~1as tx·~:~awd ,;ith aurcoi!\Ycin, ThE chest. pain and dyspnea becarre more severe <::nd a chest film showed the pr.,sunce of pleural fluid (films not available ) ,

On admission to Long Hospital, February 7, 1953, he ~1as acut<l'ly ill, cyanotic, and had l abored respirati ons . l~oist rales and r·honchi •..Jere heard throughout both lung fields , T!w urinary blad11<..r was pal pable obovo the s,ympnysis . The prostate was enlarged and firm. Laboratory u~~minations included co2 = 67 vol.%; NP~ :: 69 mg.%; wbc = 21, 900 with 97% polys , He expired the following day ,

At autopsy the lungs weighed 3250 grams, The p~eural spaces were obliterated by fibrous adhesions , Numorous milia ry white and gray- white l esions were pr esent in all lung fiel ds , The hiler lymph nodes wore en­larged, The prostate ~ras firm and large, and on section contained numerous yellow nodules from ~lhich n small amou!'lt of material could be ey.pressed,

Un£ortuna t e l y , no cultures Here made,

Case 2 A6551

SubMitted by: Department of Pathology Indiana Uni v . School of Y.edicine

This three- months- old male infant h:ld been ill f'or three weeks, It was born at eight months gestation and was small, The infant was breast£ed f or three weeks but did not gain weight, Tho~ wns no history of diarrhea , Three siblings were alive and well. Tho fami.ly liv~.>d on a farm and drank well water, The infant 1~as malnourished, pOOl'lY devel oped, and acutt~ly ill, The liver was palpated two f'ingor-breaJ ths below the costal margin, as 1¥aS the sple~n . The day following admission the patient had a small tar1y stool, Three days after ad:llssion the marrow was aspirakd . He was treated with ethyl vanillate <l.nd wnole blood transfusions, Th'?rc was leukopenia through­out the infant•s hospita.l st~ . ~n~ pnti~nt continued to have fever and died two weeks after admission,

1\t a utc,psy the liver, spleen, and l ymph nodes were enlarged ,

3 Submitted b,r : £~6~5 Indi:lno. Univ. School of l<kluicino

n epa rtlll3nt of pathol ogy Thi s 29 year ol d white housewife was admitted to t he rwdical servi ce

on Sept ombor 14, 1952, i .n a semicomatose conditi on, Two months pr i or to admissi on a diagnosis of ~iabJtc3 rnell~tu~ haJ ~con rno:e, and she wls controlled sat i s factorily by dLt<ny .;an:.gerocmt nlone . (n September 10 she compl nined of a sudden ch i ll an..l ovor the next t 1ve::.ve hours gradually beca me comatose . L>ho was t r &:Jtc 1 f ur •:iaLot,i c ac:!.~\<JsiE an;! twelve hours l ate r was rctional an1. rn-arkodl)' ir+>r cvt.d. 0:1 ~epte.li.>er 1 2 shu a6ai n be­came coroto~e o.nd was agai n tr"awi for :lci<!osis,

on admissi cn to the hczpital she wa:; s'uupc.r ous and t hure •;~a s slight generalized edoma. :::ni ti'll l ni:loratory stut!ios ~:e re as f(,lloHs : NPN = 98 mgms. %, Pl ocl Suga r = 225 mg,n .%, co2 Combini ng Pmi\lr = 2) vols, )b, WEC = 2) , 000 wi th a shift t c, the left, ROC == 3,4 million a n.: Hgb = l L.O 0"111%, A l umbar puncture was negative except for a slig~t incr~ase in pr e ssure. Two subsequent l urnb&r f:Unc t uros shc1-1ed a sli eht incre.:~ se in white cells,

Ove r t he ioll01~ing t'•IO dnys t he po.tiont bec~me m.ore r esp ons i ve and was able t o t ake or al f eedings , On t he f ourth hcspi tal day par alysis of the seventh cranial nor •;e was noted and th<: f cllwing day pr opt osis had bE.c0!113 bilateral. She gradually l ost cc.nscicusnc.ss an:! died e l even days after onset of her illness.

Autc>psy findin[\S inclu,i ed pr cpt csi s of both eyes. Localized a r eas of s oftening Here pr esunt ove r t ho ce rebral hemisphor os , The right i n tor ool caroti d artery and i ts br anches were dis tended by r ed- gray thrombus ,

Case 4 SI'68.359

Submitwd b,r: Indiana Univ, School of Matlicine 1leparttTent of Pathol ogy

This 12 year old whi te onle was well unti l September 1952 ~Ihen he noted a " sore" on his right a r m just below tho elbow, Later anothur l esi on appear ed a bove the rir~ht elbc;-,,, ~nd then anothe r lesion f ormed i n t he same ar ea , Tho bcy- l i ved on a far:n i n Indiana. His ch11st X- r ay was nor mal . In Har ch 1953 one of t l•e l esions was excisod a nd cultures f or fungi were made, The secti cns .:~rc. f r om this l~sicn,

Case 5 SP51818

Submi t ted by : I ruli:lna Uni v , School of Medicine Dc;..a .-i,mcnt of pathology

This 59 year cld white male w~s a far~r in Kcntncky until 9 year s ago when he star t od to work as 3n ac¥l pickl e r f or me t al pr~Jucts . In April 1953 he not ed a pi nlpl e on the l \.f t side of his n ose at t he muco­cut aneous juncti on. Th i s l esion enl a rgo:i , itched and burned. In october 1953 he received X- ray therapy t.c his nose·, % November 1953 a portion of t he l eft ala had sl oughed , A bicpsy was taken from the lef t ala of t he nose .

C:~se 6 SP68240

Submitted by: Indian.~ Univ, School cf ¥edicine 03mJ.'tment of Pa. thology

A 20-year-olc; Hh i t e m?.n W"ls admitted on 3/5i53 bec <.use of a mass ·palpat ed in the l e ft axilla , }!e had hac s or eness in h.is l eft shoulder a 1~eek before aciJnj.ssion and .:.t t ha t ti.ne !Bd not ice 1 the mass ,

Tr.e patie nt had h:!d rheUmi!ti c f<.:V8i ' when 8 year s old and aga i n l~hen 13. The diagnosi s of m:i.tr·a l stenosis arti in&u.f iic i ency and aortic stE:nosis and insufficie ncy hAd boen mad<: " year buf'or·e admissi !.ln. T)!r8e months before admission he haG. marr ied a g).rl :.~he h;;.d thr-ee cats •

. Physical examination e-n nd.missi,•n rc•ieal ed a firm mass in the l eft axilla .measuring 2 x 2 e m,

On 3/7/53 this mass ·was excisd ,

Case 7 S.P75419

Submitted by' : Indi a na Uni v . School of l1';dicine '!Japa r•t :.Bnt of Pat hol ogy

A 49-year - ol d white -femal e •,;ar; M mittcd to thE> hr.·sp i t<ll b0cause of weakness. Thi s had begun 5 mcnths b.:f o1•e a'Clmission follcwing a t rip t o Kentuck'.r, whe re she drank cistern Na'Lor, Shm·tly after he r symptoms began, she •t~as admitted to t he local .hospital , She v1as given penicillin for 6 days ; A palpable spleen Has noted , Following he r {li schar ge from tbe lccal hospital she continued to have fever .

'l"hc pat ient had ah;ays been in good health, dr a nk we l l v1ater a n:.i r aw 1nillc,

O:ib(; li Vt:)d on a farm .and

Physi cal examination r-n admissi on r e vealed an obese 1~oman, The blood pressure was 160/100. Both spleen ahd liver ;ro1·e palpated J em. l!elow the cost."ll mar gins . No lymphadenopathy Has noted,

Agglutination t ests f <Or S. typhcsa and Brucella abortis were negative, A chest X- r ay reveal ed slight e nl a rgement of the heart; the lung fields ••ere cl ear, Firs t and seccnd strength PPD•s 1-:er e necative as o,;as t he h istoplasm:i.n skin test. The white bl cod cell count was .3250 •·rith 38 polys; 58 lymphcc,y·t,es, and 4 mcnocytc;s; the1·e l·tere 10.7 gms hgb%, ·t he r ed ce:).l s nu.ml;>ared ;1,84 milli on •,;i th bbt\;een 6 a ntl 10 reticulated r ed cells per hundred ~rhitc cells .. A bone marrow examir~Rtic-n r eve<':l ed panhypt;rplasia , Live r ful1Ction tests r evealed a t hymol t urbi:iity of 10.5 units and a: t ot al biliru':>in of l,l mgm, %. The patient was afebrile tl>..rc:ughout her hospital stay. On 1/31/55, a spl enoctoll\Y and liver bi opsy 1-rer e dcne.

The patient •s Hhite blood count cnE: ~-reek af·~er cpamti on was 12, 100, ~lith 69 pol ys, 11 lymphocy t es, <:.n:.l 20 monCX'ytc.s. J,ll l i ver f unct i on t ests perfor med ~rerc vd.t h:L."l n0r mal limits. The re,l bl oC.:, count was 3,35, wi th 2% r eticulaoytes . FC'll c;Iing operation the pati ent's S'.fmpt cms of ~;eakness and tiredness _Usappear €,:i c ompl ewly ,

Ei !;ht mon+,hs a f t.er operatil)n the )?ati ent appeared t o be in excellent health. Her whit e blocd c(..unt wa3 17, 800,. with a normal dif ferenti al, her red blood count was 5. 33 million, her hemogl obin was 14. 5; t he reticulocyte count ;m.s 1 . 2%.

Caso 6 Submit t ed by: SP7,09'7 I nd i<::n.a Univ. School of •'1e<licine P7 386 Dopat"t m'&nt of Patholcgy

This infant was fir st adm.i.tted t o tho hospit~l wrJCln 18 '.lays old because of a generalized r a s:1, pre sent since IJirth. Shu X\d ii.rrr. large l;rz•ph nf'des in the neck, a palpable liver and splee~1, a nd a gene:-alj_zed. maculopapula r rash, A skin bi cpsy W'lS t;,.ken at til<:t tims, The in:fan-:. was dischar .::;ed, a bout one mcnth after admis sion, slit;htly i ;ll!n cv<d, :.ut socn tl:Y~ rash bcca112 worse . ?etechize bet<;an t c a ;lpear in th<3 skin, The infant also dovel cpod vomiting spells , She was re~dmitted to the h~spital when b 1/2 mcnths old, On artnti.ss i on, the infant •s temperature wa ~> 102° . Th" infant seemud well nourished. There v:ere ccchyr.1os<;s in ·t ho si ncivn , Tho liver 1vas ~;mlarged t o 1 em, a bove t he umt.iJ.i cus , The spl rmn was also palpated 2 om. bGl ow the costnl margin, The lymph n o:.les ~rore enl arred ,

The white count was 13,200 with a slight increase in number of pol ys; the hemcglcbin was 16 gms. %,

A lymph node biopsy was t ":J..en frc.m th.1 axilla ( SP 75,095). X- ray exzminations r evealed nrultiple r oun-:1 rad i olucent defects

throughout the cranial Yault and !llaih:!i bl e , A pa:ronchy~l infilt ration in the right upper lung fie;l d sugbestiv.; of pr.elll'lonia ~o:as also pre sent ,

The infant became rnoro irritable , l evt..l opod ~runting respiraticn, and di ed two weeks after h9r fin~l hos pital admission ,

At aut opsy the liver a nd si'leen were l art;c as wa ll as the lymph nodes , Thoro •,ras a scal y pe t echial rash of the entire bcdy ,

Case 9 SP7lb2)

SuLmittcd by: Ind iana Univ, School of Medicine J>:lthology Departm::nt

This 24 year old white ~•le lived in Ltuisian~ until 1947 and then moved t o Texas. In 1?'0 he mc.ved tc In~iam1 1-1h.:::r o he has >tcrkeJ in an automobile body plant.. on Jnnuary 1952 he deve l oped a n eruption of red, rins ··l:i.ko, maculopapuJ a.r lcsicn:; en his f ace , 1' hj.s later involved the trunl<~ thighs, and buttuckt>, His skin ::.eccme t.h:lcker and he noticed en­largo~nt of his nose, Thu cl re:;t X- ray ,,,as nurmo.l and the ~b.zzini t est was ne (lative, A skin bicpsy was taken from t:10 l..uttocks ,

Case 10 SP7306)

Submitted Py: Jn<ti.nna Uni v. school of Ma:!icine Dop'lr t !ll(':u: of pathology

This 1)-year-ol d m11l e from I r ak carne t o this ccu:1tty to have a cleft pal ate t'E.paired. :3hcrtly nft er his arr ival in HI\Y 19"54 he developed tuberculous ~nin,;itl.s. Thi s dil:tgnosis Has confirmed. by t wo spinal nuid cw.t•w ... ·• On aritd.ss 1on a n eleva t ed !IW.SS 2.5 :r. 1.5 em. •,ras not ed on the di.s t nl medial s=face of the rig ht f cr e.:J.rm, and a secc..nd s imil a r skin l esion o.S x 0,5 em. was noted over the !il3-:!ial surface of the right thigh, The skin lesion on the f oreann was excised durinc his convalescence ,

Case ll SI'$6603

Submi+.ted by: Ind1anr• Ul"iv. l:ichool of .-fo:licine Depo.rtment of Pathology

This 47 yda:r cH white: male 1:as cut in tho f.:ce by a f1ac:-~scent J.i:;ht tube in necu!'".bor l9!t8. The wound. W% sdurvd, but di.:l not. he;ll pl 'Opc.rl;f , Aft'lr 3 - 4 MOS, he receiveJ t bre(; X-rny tre2t1ili!nts t o t he ~roil of injury, Follc.wing tl..'.s t.~u'l.i.ns:1t moot of tlw W >ULVi. hea:i.e1, but some drainage pel'~Jisted , In April J.950 tha 11 em, scar H1?.S e:<cir.ed and oh) arua healed well, The sections are frcm this excised scar,

Case 12 5.?75600.

Su':.mitte:! by: InJiaM Uni.v, School of l,\3dicine Dep'l:r.tJOOnt of Pathol ogy

This 23 yaa r ol::'. •,;hite nurse was admit ted co Febrwry 10, 1955, beco.use cf a. "coin" lesion in too ri!,ht lun,; tli.scrvered in a r cutine X-ray examim'l.tic.n. This l e:sic.n n:;asure<:: 2.5 em, in :lia~rutcr l:n;!. was located in ths r i :;.'rt mirldle lobe or pcssLly in the lc.war port.ic,n of the right upper lobe, 'fht'lN was a l so a sol itary Ghon ccmrlox vn the rit,bt. Pla nigrams of the l esion suggeste ·1 ct'.vit~''i?n. but nn c2loium was seon.,

L:lbc;.-:Jtory fi.n.;in,;s c.nd p!!ysi.c'll oxarr.in?.ticna •,ro r e w?_thin not·mql lwts" On rotxu".'r'J 2.i.1 >1 wcige n;sectJ.on of too lung incl~:!int t.hil lesion was dorie. Tte lung cout.':li::ed a cavil!';, l.S em. in :li.an:etl}r, i.'1 •.:hich there was a gray liq·;:l.d. Tho cl:vity ~ms linud ':;y r ag&ad yellow- rrc.y tissue , No gr owth ;ro.s out.nined on cultUl'e of this material f e-r fungi and acid-fast bacill:i. Tu~rculin skin t est was negative } histoplasmin test was positive .

Case 13 Llh28

Sul:.nitted by : Indic.na Univ. Schc·ol of Medicine Departrr.ent of pa:tho:ogy

This 4?.-yoar - old man was admitted on .3/13/42 wj:(,'h collll?lai~ts of extreme •.:eaknoss, a hacki.ng c cugh, and bladder incont.inerue • H;.s sympt 1ms app.•.rentl> beg,\u i n /m~:ust of 19/.U. when he bad vo••dti1~3 a;rl di.'IITilea f or 3 we9k!:, In !luver.;~r cf J.9h.l he hP.1 chills and f " ver wl'ti.')h las•ecJ f or 3 Jo.'Oe~~s. FC'll.-•o~i.ng t his, he hc:d weakness but n o ether S'.)"mpt.om until one mont h before admiasion, when he .:levol oped a hachi'Jg' cou&h and .incontinence of. h1s bl adde:r, He• thun davolcp~d swelling of his f eet and ankl es, and becal11'! unable t o lie flat because of the cough,

Pnysical examinati on en artmissicn on 3/20/L2 re7Go.led r a les in both lung ~ases. Tile liver extended down to the umbili.cns. Pittin~ edema was present ovu r both ankles. Tendon reflexes were absent bilaterally,

Lator>~~. ory .fmdings : S'J:roJ.ogical •.osts for syphilis positive . H~ror,lohin ·= 6o5 RJJ: :: J.,OO ;r.ill:!.on Wrt; •· lt.,;;O'J w1.th a moi€;rato shi!t to the left. S~utum cUltures for acid fast organ isms = negative. A[iglutina t i ons :

Typhoid "0" = 1:60 Paratyphoid "H" = l: 8o Paratyphoid A and B = negative Brucella Abortus -= negative

X- ray studies revealed a c olle€tion of fluid in the right chest with sore parenchymatous infiltra t i on and a small amount o£ fluid in the l e f t ches t ._

Case 14 12371

Submitted bj' : Indiana Uni-v, School of Hedicine Dep?.rtment of Pathol ogy

This 77-year- old man entered tho hospital with complaints of a '' severe chest cold11 , This 11c old" apparentl y te~;an on 11/25/48 with a productive cough, On this day.., the patient had killed and skinned s eire r abbits, An ul~er developed on the back of the l Gft h<md which ~1as not accompanied by lymphadenopathy,

Peysical exami.nat i on en admi ssion vn 12/5/48 r evealed an acutely ill, slightly wasted man, Diminished br eath sounds and coarse r ales were heard ever bot h bases, A f riction rut; ''las heard a t the r i ght base,

Ther e was an ulcer 1 em, i n d iall¥ilter on the l.J<:<ck of t he left hand, Ten t o 15 pus eells were pres,;mt in the urine on admissio!l. The hgb was 13; the rbc was 3,04 million; t he ~1lic r anged f r om 5500 t o S600, Agglutin<~ticns done on 12/6 ~1ere negative f or Pasteurella tularen~>is and f or typhoid. paratyphoid, and Bi'ucella o An X- ray sh0wM a fibr otic ·nnss in the right apex ~lhich shc;•ed no change f r om that of a year pr .. viously, There was a pleural effusion and pneumcnitis in t he ~ .. !t l ung.

For the first 9 day·s of his hospital residence the patient •s clinica l picture chan[;;ed l ittle. He had a l o~1 spi king feve r v:hich r esponded scm9 -what t o penicillin. On 12/14/48 he devel ,)ped severe r espiratory distress and ~1as placed in c·xygen. This became increasingly sever e . The pati ent died on 12/15/48.

Case 15 SP72485

Submitt-ed by: Indiana Univ. School of l·Sadicine Department of Pat hology

Four months bef-ore deat h, this 48 year old man devel oped lo~1 tack pain following heavy l ift ing, He also developed sev&r e front al headaches , f he se did not improve during t he next few !·leeks . Two months bef or e ':Iea t h he had a s inus oper ati on, Follo~rinr:; the opera ticn, he de-.rel cpoed periodic episcdes of vomiting, The headaches became more severe , He also deve l oped long attacks of hiccoughs.

Peysi cal eY.amiriat ion on admissic'n t .o the hospital appr cximatGJl y 3 tl8eks before death revealed papilledema, .~ neurologica l e;.aminat i on revealed slow­ing in rapid alternating movel83nts , Urinalyses wer e negative ; t he •rhitEl c ount was slightly elevated. Spinal fluid re vea l ed c ounts ·of 25,361, and 45, mos t of the cells being l ymphocyte s, A chest X- ray showed an infilt rati ve l esion i n t,he lower lol::.e of t he r ight lung , A ventriculogram r eveal ed bilateral dilation of the l at er a l ventricles.

During the next two 1•eeks, t h& pati ent leca me di soriented, and finally semi-comatose . His intracranial pressure r anged from. 300- 400 mm. H20. A posterior fossa explor ation Has perfN·med t he day bef or e death. A small amount c f so!~, gelatinous materi al was r~moved , A left nepbrecto~ and vent r iculcureter ostomy Here a l s o perf or med , He died on April 23, 1954,

At autopsy the low0r l obe of t he l.'ight lung •t~as firm, non- crepitant, and on section clark red and eel a tincus. EXudate was present over the l a t e ral and i nfer ior aspe·cts of th" brain,

Case 16 4ll02

Submitt ed by: Dr. At~'S Quadr os da Silva at s. Casa de Misericordia Curitaba, Far.:>.na, Brazil

A hS year dd white han.-1 wc-r6er was adlllit.ted to a hosvital in Brazil, South t.merica cc:nphining of ~a1ac!J,s, gcD<.ral malaise arri slirht. woight loss. E;mmination ;=~emitted a diagnosis oi 11 Lra in t\llllor11 , - supported L-y ceral;,ral am;i o<;r.>.phy and ventriculc{lra;Jhy. At surgery a no:lular, yollo~lish mass, with l cbula'Ud c untvurs was removed frr.m the r ight parietal lobe . Grossly, it roasured 6 . 0 Ly S.o by 5.0 em. , 11ith a l obulated nodular. outer surface, which was yell C'INish-~Thite; on thu cut surface thare was an out&r portion of sclid yello~1 tissue, r.:;nging from 1,0 tc 2.5 em. Llending indistinctl ;r with a CN'C of viscid, Hhito material . The tissue sul.nnitted is from this mass,

Case 17 5011

SuLmitted by: Dr. At.~·s Quadros da Silva at s. Casa de !1isericordia CuritC\])a1 Parana, B:t•azil

A 46 year old •,Thite faroor was admitted to the Sanatoria Medico­Cirurgico do Pcrt.ao in Curitiba, Parana, Brazil, s. :.. , 27/l/53, chronically ill, ccmplaining of prcductiv.:: cc•ugh of l e>ng :!uraticn, weakness 1 and loss of weight , On admission the axillary temperature was 99 degrees F. Pulse 100 ? • minute . There was a discretu, C:a rl:. pi;ynent.aticn cf the forearws and p~nds, and extreme emaciation. Sputum examinati~n was negative for acid- fast bacilli. X- ray of the chest sh~wed diffuse infiltrating lesions bilator ally, compatit,lo Hith the diagnosis of pulmC'nary tul..e rculosis . The patient r an a fe~rile courso and cirod on tho 42n.:l hospital •lily. Ncoro;:>sy

·revealed fine nodules in l.lvth lun.;s . Bvt h arh·ono.ls 1.;erc onlarg<Jd 1 each ooasurinf: 10 l;y 6 by 5 em. be in!? the site <1f d iffuse necr csis . S,Jecirnen is of the left adrenal .

cr.so 18 Submitted by: F-216 Dr, Rceel' D, Baker

A f ifty- i'ive-year- ol d colored male had tho onsat of his disease i n July, 1946, seven years before dt~a th, when he noted f'noMxi", 14&aknoss and a we igj:lt less of ton pou.'lds, ar-.d cour;h. At th~t tim:) tJe was in the: !.rlrrf and stationed in Cali.for:~ia , ila \·:as told that X··rays sh.:-wel an infiltrate in his l eft lunr, an<: he uas transfor:r>3C: t c. a :los.,itl:.l in Colorad£,, All sputum exami•1aticne at thnt ti1oo werc;, ns,;"tive f c.r acil1-fast organisms . There was no elav'!ltion of temperatuN and his c C'ugh 1m;orovud while h.;, was hospi tal­ized, ~lhne in t.his hospit:.:l l'lfJ devel oped ::m abscess in his thoracic spL'le . Ho was disch.o:rgel ln July of 19h6.

Ev «<.s ad;n:i.ttc:i to a hospit.Jl in Scr th Carclina in Ncvember, 1947. There was temerres3 to pressure ovor the thoracc- lucl.ar S?ine :.oo lil'".itation of motion cf t!le spine , X- rcys shc.wed clvll'ii.ng of ~oth a;..io-.s c.f thfl lun;;s and a paraverte1r~.l shadc.w thou~ht tl' 1e due to :m at,scess, Re~Jar.ted examinations of the sputum f or acid- fast or ganisne wer e negative. , He rece ived tv10 c ourses of s t r-.;,ptonwcin and PAS and ~ms discharged , improved, in June, 1949 .

In January, 1950, a swelling of t he upper back l:.ecame nuctur.nt am began to drain pus. He was in a Vir~,;inia hospital durL11g 1950.

He was finally admitted to a North t.:ar olina hCISpit;:;l the day hcfore death, in extremis , There were drainin£ sinuses ovor tho l eft intEJrsca:;ml ar area and obliquely above tho ri&ht neck. Thsru was li."liktitn of motion and tendernes s of tho S[lino. Chest X- rays shevled ol1 fibr :lsis . Films of the spine showed marked ossification c-f b.;;anx::nts nni sc l e r ot ic r eecti t'n a bout the cervi cal and thoracic vertebrae . Se>f t tissue m<1ss a r wnd T-9, 8 and 7 was thought to to an abscess . No bene <'.estn1cticn n C>te<=. ,

At necropsy the cervical sinuses were shown t<. ColllliUllicate with a thick-walle~ cavity, 2 em .• in d:I.J.meter, '>t the apex cf too right lung. &.th lungs ccntained nodules a f ew :nilliJnetors in diaroter , just visible to t he nnkcd cya, and those woro most cvnspicucus in the l eft upper l ol..e, from which the semi nar slide C olll'~s . G'.randation tissue lined t hrJ pnravcrteLral absces~t.

rhe kilnoys presented diffus~ subacute [l~merulonephritas microscopically, and this was thought to i;e the rm.in factor in causing death,

Case 19 Sui;mitted by: F- 267 Dr. Roger D. Eaker

A tYTenty- fiw -year - ol d ;;hito man had ccur:;h, hemoptys i s and pain on the left side of his chest durin~ ti1e three weks prier t c death, A diagnosis of acute myelocenous l eukemia h.:ld been lll:!de previous]¥ on the basis of smears of blood and of bene I!E?.rrc.w, T~re was pancytrpcnia for two t o three months terminally and the phtelet count was not abovo 20,000. At aut opsy there was purp=, petechi ae in skin anrl kidneys, splenomegal y (750 gms, ) , and the microscopic features of ccute lcuko!n:i..:l ,

The speciol findings at autc-psy, h morovor, were thrombosi s of the l eft pulmonary artery and left supori or pulmct~<.'>I".f vein and mo.ssive infarction of the left upper lobe and p<J.tchy infarctim of tho left lower l obe of the l ungs , The pulmonary thronbus was pale pink with a &ray cast rather than the usual r eddish brown.

No cultures wo:re taken of the thrombus at autopsy and all the pulmonary tissue was pl aced in fixing fluid ,

Case 20 Submitted by: F-263 Dr. f, oeer D. Baker

A sixty- YJ3a·r-oB. 14hite widc~1 was hospitalized i.h ? J.cr i da, ten Heeks antemortem, because of mal aise of six veeks 1 durati on and f e:1ar cf one week 1 s J uro.tiun. 'l'h;Jr e was a hist < r; of f requent rospirat~ry infiJctic.ns , A s l ight hemoptysis had occurr ed nine ~-~ars pr (:!vi ously anc~ X-rays t aken then Her e said to sho~r fibrosis.

In t he hospi t al tho pt.tient had. s;>ikiug f ove r a:1d expoc tor at::Jd rusty and pt'rllL<:nr.. sp'Jt un. l'seuu< 110n~.s P.ernginosa was cclttlrod from the s;mtum. On a c o!l\binc.tion of er>Jthroliwcin and s ulfa she finally i..oCMle a f ebrile . SputuJn d i.'llini:':hccl , aez·ation oi left l vn;;; i luprcV•1tl; :nm she ~ras discharged six ·~reakq antemort em, Sho r -..:turne\i t c the hospital t&n dllys la:to~. Three ;1eej<s before death she wa s d..:;sc1·it-ed as cbes':l aald ch:ronica.lly i ll. Temper a­ture Has 103° F. She expector ated bl..,o:i·-staine·l sputum. IH:G 3,240.,000 and HB:: 14,250. Diif.: 93~-\ polys •rit h a shift to the left. Repeated hloo:l culture reveal ed no gr oHt h. Sputum cultures g:h.:'" out Neisseria, B. coli,. B. pr ot eus, I~. t etragenr1 , H. in11.uenzae anc~ pneumococci, On th;l basis of sensit ivity t est s Polymixin B 'tlP.S administered. Spu·tum s amples and .a speci men takOl') a t bronchosc'O;)Y wer !J ne!;~ti,·e for acid- fast orgaru.sms and rr.alignant cells. Chest X-ray a Heek befor.; dt::at h snou the entire left t hor ax to be opnque , Str eptomycin, sulfa, penicill in and K 1 'tlere a·i:ninis• tered with no clinica l i mprovement . The spu-tum \vas C<'ntj.nuously copious ~orith no detectable odor and with varying amounts of b l ood . Fever c ontinued t o sho>l spikes to 101 to 1040 F . Death occurred w-ith dyspnea, cyanosis and a shock--like sta t e ,

At autopsy a confluent lc:l-ular pneur.1onia of t ho l eft l c.•re r lobe, minimal bilat&ral l<:bular pneumonia, an abscess of a kirlney and hemorrhagic infarcts of the spl een Here f ound, 1\ sectic.n f r cm t h" loft lUI"-6 is submitted, The tiSS\le reaction in the a bscess of the- 1<idnoy '"as sintilar ~c that i n the l ung, except that pcJ.ymorphonuclears >·Jere- mere numerous,

Case 2-1 Snl 'mi tted by : F- 264 D1•, fl.cger D. B!tker

A sixty- three-year- ol d \4hi te woman \-las fuund t r. have chr onic al eukemic I!Velogenc•us leukemia, six months antemor t em, She 1~a s treated ~lith 6 -me r capt opurino, ACTH, cor tisone, and ant ibiotics.

At autopS'J the features of' leukemia 1-rere noted. In addition the esophagus ~ras ulce r at ed up to a l evel aLcut 4 em. belc·~r the larynx. In tho ascending colen ther e was an ulcer 7 mm. j_n :ii 2.met er. Tho U!)per surface of the t ongue shoHed a 2 em., irreg~Jb.r, rai sed ,Jlaque vii th central ul ceration, deep blue as a resclt of l ocal me'l icat icn, &Jctions cf t hr: 11lcer of the tongue and of the min.ute ulcer of the colch c ontainc:cl organ:t.ems similar t o t hose set.Jn in the scm~.nar slide ·f:r o'm tho ulc&r·at e.d esophagus,

Autopsy bact,e riolcGY ,save t.he following results : Heart blood : no organt s Mfi s een :i.n s.moars ., ~ulture ne:gative; luhg: rL.o orga_pisnls in smears , culture .. n.::.J fu.'.b~roids ' spl oen: no cr gani sl1lS in snx;ars , cult u res oog;:>.t.i ve ; intes ti.."lc s, no smear s made, cul t ures - Aer obacter aerogenos, Pseuclomonas aer ugi nosa_. :93ta hemolytic enter<.coccus> Candioa sp. No acid- fast or ganisms Here cultured from hilar l ymph nodes or l ung,

Section of lo\4Cr espobagus for tliagnosis.

Case 22 Submitted by: F- 238 Dr. Rl~r,er D. Baker

A se"VBnteen~year- old, rural boy in Kentucky ~~as f'c,und t o hav8 a l e s i on of the l ower l obe of his l eft lung , when r outine chest X- ray w~s made, The left l o•rer l obe was removed surgically, and t he puti ont m.'ldc an uneventful recovery a nd see~red entirely well t hr ee ;meks aft e r operati on ,

Skin t ests ~mre r epor ted as positive for Histo!)lasma and negative f or Cryptoccqcus.

Gr oss l y the entir<~ l obe ;ras said to l:.e invc.lvetl i n a consolidating lesi on with multipl e avscosse s .

1.

2.

6.

7.

B.

10.

n .

12.

~.

15.

16.

17.

18.

19.

20.

21.

22.

Diagnoses

Retain first ccpy cf your di ::f!lcses. It will a i d in the discussion if you will submit a copy cf your tliaOloses to Dr . B3ker prior t o the n:eetin(! · Your list need not l .. sirm.d.

1 ,

2,

3.

~ .

5.

6.

7.

8.

9.

10 ,

11.

12,

13.

11.

15.

16.

17.

18.

19.

21.

22,

Diagnoses

Retain first ccpy cf your •.li.a rnoses, It will aid in the discussion if you will sut:nit a Co// of y our d iacnosos t o Dr, Baker prior to the meetina. Your list need not 1a signed,