ARTHUR PURDY STOUT SOC IETY

EIGHTEENTH ANNUAL 5~111HAR

ON

TUMORS OF CHILDREN

New York, N. Y.

June 19, 1965 -

ARTHUR PUROY STOUT SOC IETY SE~I IIli\R No. 18

tlc:w York, N. Y. June 19 , 1965

Int roduction. Th is Seminar will differ to some extent from its

predecessors. In the f irst place i t is devoted entirely to tumors de­

ve loping in infancy and childhood and In the second p lace, sfnce the

case5 were not scloctad pri marj ly because of the di f ficulty In naming

t hem correct ly but, In several instances, because they afford •n

opportunlty t o discuss certa in featur~s that are debatab le for one

re~son or another . A correct d ia gnosis Is not enough in itself unless

It conveys a complete eoo-;p rehension of blolog ic.aJbehavJor under al l

c1 rcumstances. I t Is s•fe to say this Is almost never the c•s• and it

is ~rticu1arty true of cr.esenchynal te.nors ln gene.ra1 and of such tuu.ors

in ch i Jdren . have to be a.,1are of thi s and generally feel it netessar-y

not on ly to mak~ a di agnosis but to exp la in j ust what that diagnosis connotes

depend ing upon age. sox, rac.e, exac,t part of the body invol ved end con­

tributing factors. I~ af ra id t hat tho v•r ious in ternational committees

that are t rying to got •1 1 the worl d to agree on and usc the t~e names

for the vari ous tumor5 a re wa sting their time, unless they c~n also get tho

vari ous na tions to agree on the b io loglee l connotations of the n~mes.

hope that in thi s sess ion we wil l have free and open discussion f rom any

person in t he audience whether m~er of the Society or guest; this i s

an open forum and we are here to clarify not to d ictate .

•

Arthur Purdy Stout Seminar 1965

Case I • Llpobl~stcmatosls of gl uteal region .

Case 2 . Granu lar' cell tu.mor of vocal cord . ./

Case J , Odontoma of mandible . v Case 4. Adencmo (sal Ivo ry gland type) of bronehu s • ./ 1\\IJ (.o)d . ~ .. )# '') o-Cas~ 5. Rhabdomyosarcoma . embryona I, of bladder. /

Case 6. Rhabdomyosarcom3, embryonal, of pre-sacrococcygeal reg ton. ,/

tase 7. Myositis ossificans progressiva. v

Case 8. Xanthogranuloma of retroperitone~ ,

(polypoid) of i l;um. • Case 9. Xanthogranu IOII'.a

Case I 0. Juvenile melanomq of auricle. v Case II , Meningioma of cerebral men inges

Ci:ISB 12 . 11 I xed Lumor of I [ ver. v

•

Case I. (PG.S-77410)

Microscopic . This is a tumor of l ipoblastie tissue that has

'ertai n strik ing f eatu res . It is c.oq:tos ed of both adult and embryona1

fat ce ll s t hat ~re collec ted in to groups enc losed wi t hin fibroblast ic

bands . Thi s fcaturo distinguishes It from tho dlf fcrontl otod lipo­

sarcoma wh ich It most nearl y resembles . Tho tumor di ffe rs £11so from

the o the r embryona l 1ipoblastic tumor, the h iberno~ . because it is

no t di s t inguished by foam cel ls.

Discus sion. I thought you a l l ought to bcccmc acqua inted wi th

th is rather rare type of erbryona l f a tty t~r which was fi rst report ed

and naoed l ipoblastomatosl s by Frank Veil los and his associates in 1958.

His case was In an 8-months-old fema le infant and was quite ext ens ive

involv ing the upper chest \-~&It. the ax illa and the adjaeent suprac lavict.:! or

area. An extens lon surrounded t he brachia l a r tery, vein and cords of the

brachial pl exus . It was d issected f ree and there was no recurrence after

19 month s . The nc.xt year fn a paper deal fng with lt pob la st!c tOJ.c"'ors of

children , Shirley Kauffman and I included fou r cose$ a ll ln !nfan ts less

th~n a yco r old and all s uccessfully trea ted 4 l thcugh one h~d a recurrence

which had to be removed .

At the present ti me we have increased the n~ber of tines th i s

diagnos is has been ~ade so that we have recorded IS clscs in chi1dren and

6 eases in adults .

C~se 1 . (eon 1 'd)

• llpobl~stomatosis in children- 15

Sex male 4. female 9, not stated 2.

~ (in years)

.2.:2 10

Loca tion

k!.2. I

Neck and axi l la 6 Thigh and gluteal 6 Back 2

Perineum I

lipoblastomatosis In adults

Sex male 4. fe.-wle 2

Aces 43 - 72

Location

Back 2 Pop I itca l 2

Mesentery Omentum

All 21 of these cases have ori g i n:.ted e l sewhere and hava come to

us as consu l tnt lons. The cases that have occurred In ch ildren are all

definite and believable. The ones t ha t have been found ln ·adults seem

more questionable to me. I think sometimes the diagnosis was suggested

in de$peration becaus~ we could not think of anything else to call it. We

need more experience before we can accept cases In adults with complete

assurance although I think some of them ~re real. In any event it is

just as rea l In chi ldren as the hibernomas; i t Is strange that most of

the latter are l n adults. We have recor ds of 17 cases of hibernoma and

only throu of t hem are in childrc.n.

•

Case I. (cont'd)

References

Kauff~n,S.L. ond Stout ,A.P . lipobl~stic tun\ors of eh1 1drcn Cancer 12:912-925: 1959.

Vctlios,f ., 8eez. ,J. and Shumacker, H.8. Lipoblostorno tosis: tumor of feta l fat dl ffercnt from hibernoma : report of iii case with observa tions on embryogenesis of hum~n adi pose tissue. Am.J.Path. 34: 1149- 1159: 1958 .

/

Case 2. (P&S-78986)

• Microscopic . This lesion in the la rynx sh~~s a marked pro-

lifera tion of t ightl y packed ce lls wi th smal l dark nucteJ and re la t ivel y

volumi nous amorphous cell bodi e s. The cytoplasm of these cel l s i s f il led

Nith small but d istinct granul es . These a r~ neutrophi l i c i n H&E. With

PAS some of the granules a re larger and appear pos i tive . The cells a re

f~nd immedi~ te ly benea th the su rface epithe lium and surround some of t he

underly ing mucosal glands . Because this specimen is only a biopsy, i t is

not possi b le to -t e ll how deepl y they extend. Uo mitoses are detected and

t here is no o r gtm.o id a rrangement of the ecl fs.

Discussion . Th1s c.ose \'Jas Incl uded for two reasons. It was not

an ti c ipated that there woul d be any diff iculty about the diagnos i s but it

~ee.med \'JOrth whi 1-e to cotrment on fi nding a gr~nu l<J r cell tumor- in the larynx

of a ch il d ~nd also to discuss the na ture of the granu la r- celt tumors in

gene r-al., In addi ti on to thi s case ~-o•e hav~ 10 benign gr<lnular cell .. tumors

o f the larynx . Eight of them ,..;er e females and on ly two were males. Fou r

of the f ema 1 es varied f rem 20 to 25 years, one l'ias 32, another was 41 and ...... t he <:lges of the other two 'trere not g iven bu t both of t hem \'Jere marrled so

that i s is improbable they were ch il dren. The t\o:o men were age 43 and 60

respectively . I n the literature I coul d fi nd on ly one case in a chi ld

(Ottosson) although I di d not make an exhaust ive s ea rch. Blskpand Wagner

reporte d on t he subject of granul a r ce-11 myob la stoma fn chi l dr en . They

found 10 cas es and added one of thei r ~~n but there was none in the larynx .

I assume they excJ uded ma l igna nt cases for I am sure there have been many

~Qre of t hese in children. Qyr own records include 11 beni gn granular cel l

tumors in ehfldfen exe lus ive of ten ~~anulaf cell amcJob lastic tumors

attached to the gums of n~~born fema le i~fants . The eleven cases in­

cluded 6 ma les and 5 fema les; only one· was in an infant ~ year s o ld. The

/

Case 2. (con t 1 d)

• r est were all 8 to 15 ye.ars of age. f i na lly t here a re the malignant

organoid granular cel l tumors or alveola r soft part sa rcomas . We have

records of 18 of th~sci n children and they are certainl y quite dif ferent

in appearance and behavior from the other two varieti e s .

I do not \'li sh to go in to the comp J ex andhhot 1 y debated prob 1 e111 of

the cellula r o ri gin of these turr.ors . I t is qu i te possible tha t none of

them I s r eally myob l astic, The ones that appear on the gums of ne\o~born

female infants are certa inly fiOt myoblastic but ameloblastic tumo rs. Sot

I am stubborn enough not to believe that the electron microscoP. ic ev idence

is suffic iently convincing to p rove that the benign tumors arc neurogenous

in or igin even though it is someti mes possibl e to fi nd grZ~nulor cel ls in-

side t he sheaths of pe:tipher~l ne rve twigs-. It is ce rtai n t hat a dis-

ti ngui shing char.;~c teri sti c of all of the vadous types is the p r-esenc.e

of gr-anu les in the ce rls ~ For this r-eason I am very rel uctant to g ive up

the adjec tive in the nomencl a ture . I have deci ded to a bandon the tenm ......

myob lastoma and subst i tute fo r it t he noncorr~ i tal t erm of t umor. Thus

shall refer to the present ease ~5 a benign granu la r cell t umor . The

mal ignant cases, I call ~lignant o rganoid gran~lar cell tumors ; and the

congenita l tumors on the gums of fema l e infan t s as congeni t al a~eJ oblastic

granular cell tumors . This \-Ji 11 please noDody but me but I think at least

pcoplo wi 11 underst<:md ..,;h.;~ t I am ta lking 2bou t.

/

•

" Case 2. {eont ' d)

Refcronces

Bishop , H. C. and \Jegner, B. i1 . Granu l .:~r cell myoblastoma in chi l dhood . Ped lotrics 19:858-862: 1957 . {no la rynx coscs)

M<lc.N,oughton, I .P.J. , and F r~ser,H . S . Myoblastoma of the l a rynx . Jour .Loryng. & Otol. 68:680-689: 1954. {no chi ldren)

Ottosson , B.G . ~yoblastoma of the larynx . Acta.Oto-laryng . 58:87-93: 1964. {boy, 9 years old)

._

Cose ) . (P&S-78987) •

Nicroscoeic. This tuiT!Or is composed of a jumble o f cementum and

dentine often arranged so as to simulate bone. It is not all bone for

some of the tissue has no cel ls In lacunae and does have the canals

characteristic of dent lne. The soft tissue spaces between the bands of

cementum and dtmtine are fi I led iii ~tJith loose fib rob lastic t issue re­

sembling pulp. At one end of the specimen some of the dent ine is cove red

by what app·ears to be a layer of enamel. In turn th is is i n contac t with

~melobl asti c tissue consisti ng of t en of a J.ayer of columna·r ameloblasts

In contact with t he enamel on one side and on the other side they rest

on the stellate reticu)u~. Sprou t ing f rom th0 ameloblasts are sometimes

cords a nd knobs such as can be found in ameloblast ic fibromas.

Discussion. I though t i t would be · o f inte rest for you to see a

nice ex9mpl e of an odontoma. It i s easy enough to recognize them both

cl inic:al ly, by xray, gro ss ly, a nd rnicr"oscopi cal l y but t hey are not often

se~n by, ...... the pa tholog i st un less he gets w..aterial f rom den tal c l inics. I n

ou r records \'ie have onl y 20 cases although ·a t one t ime we got a gr eat dea l

Of th·e s urgical ma t erial from the dental c l inic. Sinco t he odontoma is

t he resul t o f a congeni ta l ma lfom.a tlon o ne might expect t hat a majority

of cases h'Ou l d man ifes t th emselves in childhood but only 7 of our 20 ca ses

are known to haVe been r emoved f r om chi ldren whose a9es var ied from 2 to

1Lt years a nd al l 7 of t hem wer e gi r ls . This co•npares \'l ith our congenital

amelob lastic gran~ Jqr cell tu~~rs of the gums al l of wh fch deve loped in

gi r ls. However , when t he cases in ol der people are i ncl ude d wi th the

chil dren we f ind 15 \'lere females and 5 wer-e males . i~ere Is a good

description of odontomas In Thoma's Oral Pathology ttnd I s ha l l o n ly make

a f ew observat ions o n t he pathology.

/

Case 3. (cont'd)

•

Since this malformation i umor alway$ develop.s a t the si te of a

missi ng tooth it is natural to ~xpect It to be composed of the various

e.lem~nts found in ~ toott, . Th i s is the case for it is ~asy to (ecogni :z.e

den t ·i ne • cementum and the tissues of the pap i II a. If one is I ucky o ne

may also be abte to recognixc enamel. If It is present one can also

recognize ame loblastic t issue. These tissues may be al l jumbl ed t ogether

or occasionally one may find a number of tiny den ticl cs that res~b l e

min iature teeth. Thoma has a number of names for t he var ious appc:a i'.::nccs

of odontoma but it seems to m~ scarcely worth .,.Jili l e to t ry to remember

these names since al l odont~s are sharply ci rcumscribed , scmetimes

encapsulated and easily removed. The only form described by him we

have not seen is the developmen t of an odontcma in the wall of a paradental

cyst. They are ~I I benign ~nd apparent ly do not lead to the formation of

malignant turr~rs although Thoma quotes cases reported in which a Sdrc~

develo~d. I \<t i 11 bel reve thfs when I see such a case. or read a convinc ing

report describing one . Bernier in his f~scic1e does not mention this

poss i b i I I ty.

Cas~ 4. (P&S 78988) •

Hicr oscooic.. Thls tumor is obv ious l y a .g-landular mucus-secreting

one. The g lands are some ti me~ tubular and often arranged in a line.

have looked c-a refu l l y but I cou ld r:ecognize no squamous ce lls in the glands

themselves , but a t one edge there are squ~mous cells In continuity w: th the

tumor . These have intercellular br idges bu t do not form ke ratin .

Discussion. Th is tuw~r has a strong resemb lance to a mucoepidermoi d

salivary g land t umor of t he wel l d i fferentiated va ri ety . I thoug~. t it wou! d

' be interesting t o indude it because it will g ive us an opportunity to

d r scuss the ques f:l.on of this type of tumor in c h i1 d ren. I t Is a I so of

interes t because it has a bullt- in falloN-up havi ng a p roved ex istence

of at least 19 years before it was fi nally removed . It be longs Nith the

group of juvenile b ronchi al ade nomas of wh ich there a re sever al va r iants .

Th is one could be cl assed as a bronchial adenoma of t h e s·al ivary glt'lnd type

or the well diffe rent fated muco-epi dermo id typ e4 Although we have many

b ror~hia t ~denomas we have only 9 other cases in chi l dren. The statistics

on th~sc is as fo11ows: female 5, ma le 4 .. Two c~ses in the f irst

qui nquenn ium, a congenital case removed a t 8 wee ks of age, and a five yQat

old boy; 2 in ·t he second quinquennium and 5 i n t he thi rd. Five of t he

cases wer e . of the carcinoid type w i t~out circ~ latory symptoms bu t the

five year oi d boy had a mutastasis in a hilar lyMph node ; the oth e r four

\'lere g landu iar but only one of these \'las mucus -secr e:tl ng . The congen ital

cas e ,.,.asoos t unusua l because i t v1as partl y papil lary . There ~ ... e re no

mucc-cp ider.noid cases 1 ike t he present one.

have long been inte rest ed in t he subject of edeno:r;:l of t he b ronchu.s

beca4se had a n oppor tunity to sec sec tions of a case in a 2~ ye~r o ld gir l

nJmed Hazel Monson '"ho had her l eft l ung r emoved by Dr. Rionhoff for.:. t umo r

•

Cose 4. (cont' d)

• of the bronchus tfovenbcr 3, 1933 and It was ~Jaimcd that this was the first

successful sur g ical cure of a c.ardnOI'I'Ia of the l ung. It was a carcinoid

type of adenoma . Dr. Evart s Graham was the first su rgeon to do~ success-

ful pneumonectomy for squamous cell earci~ of a bronchus In Apr i1 1933 .

The l iterature regardi ng bronchial aden~ is most interest ing al·

though extreme ly confus rng . In the ear ly days there wa s a groat deal of

$~ulatlon regarding the cell ular orig in of bronchial adenomas. Host of

it was pretty puer i l e but It fi nal ly boil ed down to the fact that a ~jority

of the tutr.ors resembl ed ea rcinoids lind the rest resetnbl ed salivary gland

tumors. There was doubt about the c•rcino id id~ unti l it was found that

an occasional bronchl~l c•rcinoid oould produc• the ~erotonin effect . Thore

was also o great deal of ~onfusion obout t he mallgnen~y of cD rc ino id tumors

and this persi sted until the large c l inics collected enough cases with

fol low- up1 to qake authorita t ive st•t~ents. The paper by Hc8urney ct al

in 1953 gives the c~pcr i ence of the Hayo CJ Jnie. One hundred ~nd eleven

' cases and nine ..,li t h metastases (8.1%) . Th.ey assembled 700 cAses from tt'la

litera ture. of which 78 naetastasizcd. In the ...,yo group al l 9 were carcinoid

type. They es timated from stud ies of other reports t hat the ca rc inoid type

metastasi tos 3 t imes more oft en than the sal ivary gland type. Hone of the

Hayo ca$e5 that ~etast~slzed wa s in 4 child .

Bronchial adenoma in childhood mu s t be re lativel y rare for V~wter

and Ferguson in repor t ing a case in 4 boy of 9-9/ 12 years could only

col lec t 20 cases . However~ I am sure thei r review of t~e li tcr~ture is

inccmploto for I know of some cases they failed to f !r.ci. In rny e..,ent, tht

youngest pllt lent known to t hem h'aS 4 years old. None of the c1ses ls known

to have metastas i zed. However, it is poss ibl e for a b :onch i~ l aden~~ in

•

Case 4 . (cont ' d)

a child to metastasize for Rosenbluth et at have reported a carcinoid

adenoma in a 12 year old gi r l that @eta5tasized to the eye and, as I have

a l ready stated, one of ovr cases had a metastasis in a hllar lymph ~e.

Reh: renccs .

Me8u f nay ,R .P., Klrkl inpJ.H., and Woolnor,L. B. Mct~stasizlng b ronchial odonomos. S.G. & o. 96:48Z- 49Z: 1953.

Rosenbluth,J. , Lava l, J ., a nd Wei i ~V . the 6yc. A. H.A.An :h.Ophtha1.

MetastGsls of bronchia l adenoma to 63:47- 50: 1960.

Vawtcr,G . F. and Ferguson,C. F. Bronchial ade~ ln childhood. Ann. Oto1 . Rhino! . & laryngol. 67: 1113·1125: 1958.

•

Case 5, (P&S 78065)

Mj croscopic. This tumor is compc5cd of cel ls that a re relatively

sma l l and either rounded or slightly elongated. Occasionally t hey have

tai l s. The cy top lasm i s neutrophil ic and no~m~re in my sections is i t

ac idophili c nor have I de tected any cross striations. Mitoses a re hard

to recogn ize but I believe th~y are qu i te numerou s for J counted 40 in

50 high pO'n'er f ields. The tumor tfssue. varfes in c.ons istency: 1oose myxoid

pa tches are scatte red freely through thC dominant soli d are.as. The

reticulin stain is inte rest ing . There are f ine reti cul in fibers every-

where, mostly curly, ·even in the solid areas where they surround every

cel l. There are also a few elongated wiry f ibe rs .

Discussion. Th is tumor has been inc luded both for i ts own sake and

also bec.~use i t will act as an openi ng wedge t o permi t d iscuss ion of a sub-

ject t hat Is of considerabl e general interest. From its situa t ion bcttvcen

t he bladder and the rectum of a 30 month old male infant, \-tith projection

Into the b I adder, it shou 1 d be. e: i ther an embryona I rhabdocnyosa rc.001a or

poss ibly a leiomyosarcoma . It does not have any suggestion of an ~bryona l

" smooth muscle tumor $0 that it shoul d be rhabdomyosarcoma. But is it?

There is extremely lit t l e evidence of rhabdOfTlyoblast ic di fferentiation ilnd

on the other hand It i s quite fibrous with its unusual number of delicate

curling reticulin fibe rs. Can it be that this is a fibrosarcoma? If it is

I never saw one like It in an infant ~or in this situation between t he

bladder and the rectun1. In spite of its lack of differentiation my choice

is ombryonal rhabdomyosarcoma.

I \·tOu I d like to use this case as an excuse for making some rett~a rks

about r habdomyosarcoma in child:ren~ . If you have thought about the subj ect

Cases. (eont ' d)

you mus t have been impressed by t he dif!erencc In &pcearance he~c~n rh~bdo-

myoserc.ocNS in adults a nd c.h!!dren a~d on the r.mrkcd ~ifferenee in the regions

involved. Tho fol10\1ing tab !e \<til! i11u:-:rate. this.

473 Ca::es of Rhabd<:Jnyoc' rr:.omt~ Adu 1:: 23-3 - ..'c\'cn i 1 c Z35

Adu ~ t ).;!:;~~ ~ Juven ile

Upper extrcmi ty ) c3'' -~ ., 5 Or b i t 0 25' ~ lower oxcrcm l ty 9• I -:: 27 fte::t o f 12 67 p Ant"!rlor :orso 28 ~ :; 5 hcod ~ neck Poster lor torso 26 J<- 1 I vro~en I t . 16 64 ...,

Rctroperit. etc . 15 i I V~sccra 1nd 9 9 Hodlastlnum 4 I unkno.-m

As be~een adults and children the death rate in adults is approxi-

mately 6)% while In children it is esti~~ted at 8~. The te~ used to

describe the' histolog ical picture are: four: Embyronal, botryoid, alveolar

and pl eomorphic. In my experience al~~st a ll of the p l c~~rph ic tumors ar~

found In adu l ts and that term expr~sscs my Idea of tho rh~bdomyosarc~~ in

adults. The other th ree terms are used to descri be the variety of rhabdo-

myvsarconDS found chiefly in children. The botryoid var iety ls found

expeclol ly In t umors that project outward from ll free sud ace. they are

extensively myxold and nodular which accounts for the grape-l ike appearance.

The alveolar tumors seldom have ~xoid areas, the cells are rounded~ of

vary ing site, s~ctices with acidophilic cytoplasm and they often g~ in

cords with an lrregu lar empty space 1n the centr• l part wh i ch gives the effect

of irregular al veolar formation to those with oct ivc imag inations. If the

hlsto1091Ca 1 pict ure is too confused or comp lex to get ei ther of these

categories . the convenient term embryonal wi ll take c~ rc of everything else .

•

Cases. (cont 'd)

How I cannot find out if there is any difference In the behavior of these

three varieties and unless ther~ is some good reason for retaining them,

it seemi to me a lot of ti~e a nd effort wil l be saved by calling all three

varieties of j uveni le rhabdomyosarcoma by the reasonabl e descriptive term

••embryonal''· These varieties were perhaps of some use when we were learn-

l ng to recognize rhabdomyosa-rcomas in chi l dren but now t htlt we have the

variations wel l fixed l n our minds why worry obcut va riations un less i t

con be demonstrated that there is some difference In behavior? There is

one featur~ of rhabdomyosarcomas In children that 15 ~~rth mentioning :

those coscs that are congenital appear to be less ~lignant than cases in

old4r children. Of 15 ease s recently studied by kauffman and Stout , 6

patients died but on ly 3 of them had metast4SeSi 8 had no metastases after

periods of 1! to nt years and one patient W.)S not fo ll O\~ed. Four of t he

8 cases th~t surv lved were unusua l because they cons isted of bvndle.s of long

sl ende r cel l s many of which had abundant eas ily detected cross- striations.

Thi s i s a var iety that l hav·e not recogni zed except in these congenftal

References.

Horn,R.C .Jr . and Enter 11ne,H.T. Rhabdom¥osarcoma - A clinicop~thological study and classific;ation of 39 cases. Concer 11:181- 199: 1958.

keuff~an ,S.l . and Stout ,A.P . Cong~ita l mesenchymal tumors . Cancer 18:46o-476: 1965.

•

Case 6. (P6S 49679)

Hlcroscoolc . This is a tumor r.~de up chiefly of ~11 rounded

cells . These vary somewhat in siz.e and tha Njorfty of them have a

scanty eytoplasm ,.;hich is not r emarkable although In some places it has

a s l ightly reddish tinge. This was sent to me 8 yea rs ago when I sti l l

had a lot to l ea rn ebout ch ildren's tumors. Af ter a great deal of

cog l to tl on I cume to the conclusion i t wD$ probab ly a mesonephric carcinoma

partly bCCGuse of cha vague alveolar arrangement of the ce ll s ~nd also

be~use of areas where the cell cytop lasm wDs clea r and had an epithelial

appea rance . l had had two other retrope r itoneal tumors in children before

this one that I thought roight qualify for that diagnosis although they did

not look very much l ike thi s one .

-01scussion . When Bob sa id that he had fol low-up inforr.»t ion and

an autopsy on this ease I made the mis take of Accept ing t he case without

looking at the s lides be lieving it was a ret roperitonea l mesoneph ri c

cerclnomo . ~/h en I got a round to looking at the s lldos it was too late

to t ry to Slve rny face by rej ec. t i ng it. Of c;ou rse no\.; I think thi s tumor

is ~n emb ryonal rhabdomyosa reoma of the Rlopollc·Horn alveol~ r type. As

I have 4llrcady exp ressed my opinion that calling it by t hat special name

makes l t neither n:ore nor less malignant than any other err.bryona l rhabdo-

myosarc~ . It only r~ins for me to di scuss with you the diagnosis .

Sinte there are cells with cross-s triations and tadpole cells the diagnos is

must be e! ther rhabdomyosareoma ot ma 1 ignant mesenchymorn. wi t h a rhabdo·

myosartometous e lement . Actual ly there Drc no other retogniz~ble elements

ol though much of the tumor ;s undifferenti ated . I would have l iked very

much to hove been able to include a good juvenll o ma l ignant rnescnchymoma

•

Casa 6. (cont'd)

In this Seminar but it means getting anough materia l so that everycne 'an

have one or more slides showing the different elemen[s ~ We have never

succeeded In doing this for any large group .

•

Case 7. (P&S 78989)

Kicroscopic. The sections from this eosc show a fibr~tous

prollforet ion of well differentiated tissue in which , in one sect ion

removed I presume f rom the scapular region there is a sma l l fragment

of d ifferentiated bone and cartilage which mtght suggest e ither pro­

liferat ion or osteochondroma.

Discuss ion. Thi s case is not diffi cu l t to diagnose in i t s

present state but I t hi nk it is Important t hat we shou ld al l realize

tho differen t conditions with which it may be confused in its early

stages . As I took ove r o~r records I find that we made a l~st all of

the mistakes concern ing the dreadful disease that i t is possible to make.

In the first place i t i s a di sease that no doubt Is caused by congenital

metabo lic aberrati ons and we have never encountered a case that f irs t

mon1fcsted Itself after age 6 yea rs . lh@rc a rc eases of progress ing and

pers ist ing ossif ication in loca l ized Drcos Jnc1uding musclos but these

deve lop l n adol escents or adults. One might bo tempted to call such

cases progress ive myos itis ossificans but sl nco they are quite different

f rom true myos it is ossi ficans progress ive t hi s on ly produces coofusion

and i t rs not a good thi ng to do . Another souree of confusion arises

from the fact that the true disease genera ll y f irst manifes ts itself by

the formation of Fibrous nodules in the corluct1 subcutaneous, or even

intremuseul•r tissues almost anywhere on the body surface. In thi s stage

before the bones become affected , t he disease has been cal led myos itis

f lbros• progressiva . In true myositis ossificans prog ress iva, there will

como a tlmG when bony bridges cQrnmence to fonm Jo in ing the vertebrae to~

gethe r, or th e il ium to the femur, the humerus co t.he ulna or radl us e tc .

and lhus st i ffen ing or irrmobil iz ing the j o int. Thfs continues unti l the

•

Case 7. (cont ' d)

patient becor.~s an adult and may be bedridden. The f lbroys stage of the

d lsdOsc l!'lay be confused wl th goner a I i zed f ibromatosl i or. when it is

solitary, \>lith s imp l e fibromatos1s . In only one of our fi ve genuine e-ases

d i d the o riginal fibrous nodules conta in any caleJ um . These nodules \\o'e r'~

most unusual because at first they were in the skin and ~ny of thEmdrOpped

off spont<H>COOs ly. But eventuolly the bony bridges began to fom . A great

~ny types of treatm~nt h~ve been tried . Excisi on of the original fibro­

motoses does not check the oss ification. If the bony bridges are exci sed

they s imply g row back aga in. Poisoni ng wi th radium, cor t ico· s teroids and

a ll other fonms of treatment have sometimes seemed to sl~~ the process but

as far as I know nothing has over effected a cure.

•

Case 8 . (P~S 54265 , 67269)

Microscopic. Thfs Is one of those tumors thot leave one c~letely

f rustrated bec~use t he ~ lstol ogJca l pic ture i s constantly changing from

f ie ld to fie ld and not hing Is c lea r cut and dec i sive . The tumor has a

grea t dea l of connective t issue In l t but certain ly It Is not a f i bro=

sareorn~ no r a fibr~~tosis. In p laces a storf fonm pattern Is evident and

one can labe l such a reas f ibrous xanthoma (or DS we now prefer) fi brous

histiocytoma. Bu t this pattern appears only occaslonelly. E l s~·here two

differen t patterns appear . There are elongated ce ll s and the f ibers a re

stra ight and wi ry , para l le ling t he long axes of the ce ll s . This patt ern

might f i t leiomyosa rcoma except tha t the ce l ls do not look too much l i ke

smooth muscle cel ls. Elsewhera tho e longa t ed cel ls a re absen t and the

fibrous background domlnatos the picture..1!"i t h rounded cells set i n it .

This vaguely suggests osteoid but it does not quite fit. Thus w~ find

ourselves frustrated and ctnnot give t he tu~~r a proper n4me. It s eems

to be~ ma lignant tumor but th is time I have been unab le to recognize any

mi toses In 50 hi gh power f lolds which is st range if tho tumor Is rea ll y

ma li gnant . Th~ t umor ce l ls a re often obscu red by t he Intense Infi ltration

of p lasma celts and ly~phocytcs . Thi s fea ture makes ft possible to thi nk

of t ·hls growth as a xanthogr•nutoma. Poss ibly that Is • more appea ling

Interpretation.

Di scuss ion. When I was firs t C·Onsu l ted about thl$ case I fc.lt

complete ly confused but a t the t ime fe l t t hat I could ~ke no ot her

suggestion t han t o ca ll I t a m~l i gnant mesenchymoma . Th is case was in·

eluded by Art egi s Nash and myself in the paper de~ I lng with mal ignant

mescnchymomas in ch i ldren . But now that I have restudied the case for

this Seminar I feel th~t we never should have included such a doubtful

cGsc. At the time when we first stud ied th is tumor we had not observed

'

Case 8. (cont 1d)

any cases of xanthogranu loma in children which may have been \-thy w0 did not

think of this poss rbJ r ty. Since then we have recognized two cases . One in

a 2! year old girl involved the rctroperitoncum. The other in an 8 months

old boy was a larg~ tumor that involved both the mesentery and mesocolon

and has very much the same -appearance a~ ~oes t his present case.

In searching the 1 i teratu re I have come across two other ca ses.

Pack and Ariel described o~ In a 5! year old ma l e. He had a finn pain·

less moss In the h:ft 11 tac region which was biopsied and cal Jed o xantho-

granuloma. The;, patient was trea ted by xrays and was \<~ell 10 years l:.ter.

The other case was reported by Krugly et a1. in a 2 yea r old white gir l .

The tumor was in the left retroperitoneal_ space. medial and enterior to the

ilio- psoas musc le. The tumor measured 2 x 5 x 3 em., , ... as biops ied and

trea ted by radiotherapy . Fourteen months later the child 111as -f ree of

symptoms .. These t\·JO cases ar.e more li ke a form of histiocytosis-x chan

the two cases in our collection.

Whil e re t roperitoneal x~n thomgranuloma is not too uncommon in

adu h s, i t is- evident that it Js exceedingly rare in children

References.

Krug!y,N., Emanuol,B . , Smallbcrg,\-1. and Hciga,S . xanthogronul omo . Pediatrics 30:608-612:

Retroperitoneal 1962.

Uash,A. and Stout,A.P. Ma l ignant mesenchymomas in children. Cancer 14:524-533: 1961.

Pack,G.T. and Ariei,I . M. Tuw~rs of the soft somat ic tissues. Hoeber & Harper, New York, 1958 . pp. 723 and 749 .

•

Case 9. (P&S 78990)

Hicroscooie. This nodule consists )4rgely of fibrous tissue with

many collagen 1nd reticulin fibers that sometimes fonm bands which are

$inuous1y lntcrtwlne.d and occasionally h3vo a storlform or rootted appear­

ance. The neck is covered wlth mucosa which gradua lly d~sappears and is

rep laced by granu lati on tissue. The whol e tumor I• lnflltr•ted by lympho­

cytes and p losmo cel ls . Those are particular ly numerous In the neck whe re

the growth sprlngs from the gut v~l l. The whol e tumor is quite vascul ar

and the general appearance resembles the retroperitonea l xanthogranoJomas .

Discussion . It seems remarkable to me that once before in these

Seminars we have had a tumor coeparable to this one In the colon of a

four•year-old boy and even more rCGarkable that It came from frank Vellios .

It was Included as Case 3 (P&S 43917) in the 19S4 Arthur Purdy Stout Society

Seminar at the A.f .I.P. in Washington, D.C. At that r::Jme I \>tas baf-fled by

it ~nd cou ld only suggost that it had a farnt rcscmb l ~nce to angioflbromo

of tho adolescent pharynx.. That was a wild shot and I beli eve no.." a very

poor one~ I got it out and studied It again and am impressed by the in­

fl:unnatory eel I clements in both lesions ine ludlng many plasma cells.

havo hunted through many papers d~allng with tumors in the sma l l

intcz tinc to s~e if 1 could find any e~arablc cases In a~u its Of children~

It is really impossible to tell because ~ny of them ore Included in large

groups Including both adults and children, while only a few deal with

chi ldren Dione. \-lhen a vague growth like this Is encountered it arouses

no lnt~rost and It is not carefully analyzed and when i llustrated it is 1m­

possible to gue~s its na ture because the illustrations do not illustrate.

One case in the i leum of a 68 year old woman was pedunculated and vaguely

•

Case 9 . (Cont' d)

re5emb l ed th is case . Lichtenstein and Dutra who reported it cal l ed it an

angiofibroma. It was composed of di f f erentia ted fibroblastic t i ssue and

many cap i II a ri es . It did not have the ~omp 1 e~ composition of the. t.,.,o tumors

we are consider ing nor the inf lammatory lnfiJtrate. Polayes and Krieger

reported a la~ge Vanek tumor In the j ejunum of a 76 yea r old male but I do

not th ink these tumors in children look at all like a Vanek tumor .

think Frank should report these th~ tumors. By ca l ling attention

to them he may s t imulate others ·to look t h tough thei r coJTcctions and

produce sonte more . Then perhaps we may learn something more about them .

Refcn::nces .

Lichtenstel n, M.E. and Dut ra,F.R. Angiofibroma of the i leum. Arch . Surg., 47:69-75: 1943. (female 68 , pedunculated and oaused Intussuscept ion/

Polayes,S.H. aod Kreiger ,J .L. J.A,M,A. 143:549-551:

-

Eosioophi I ic granvloma of the jejunum. 1950. (mole 76).

Coso 10, (P&S 78991)

M1croscooic. This tuw~r cOnsists of small groups, short cords

and sometimes single cells growing in the papillary layer and t~e super­

ficial pa rt of the cor ium. The cells are quite large lfJi t h large nucleol i.

In one sect ion a few of these s ingle cells are in the epidermis . A con-

side r~b l e number of them are multinucleate. h~ve not recognized any

pig~nt in the t umor cells . Although there are cel ls in the epidennis none

has penetrated through to the kera t lnJze-d layer. I have looked at all of

the ce II s in my s 1 ide and have not re.cogn i zed any mi tos es . The re are so

many haIr fo IIi c I cs in the grO\ ... th t hat I imagine it mus t have appeared 1 ike

a hairy na<!vus .

Discussion . I presume lauren put this case in the Seminar because he

wanted us to discuss the question of the possibility of malignancy In p ig­

mented tumors In children. I \velc9rne· this because ft usu~!ly ar.ouses p!enty

of debate. Before I discuss the diagnosis in this case t wouid l ike to

give you a resume of our experience with potentia l ly ma l ignant melancrnas

in children Jess than 16 years of age. I find that we had 70 cases that

h<;Jve been classi,Fied as juvenlle melanomas. That diagnosis includes all

of t he cllses that are not obviously benign p!~ented moles. Althoug'h t\le

hav~ not m.::de o:~ny re<l l attcll".pt to fo l lcM these cases, it happens that we

have some fo 11 ~·-up i nforiT-'l t ion wh l ch is of i n<:eres t ar.d , in any even t , the

s tAtist ics concerning these cases is of consldefable jnterest to me and

perhaps i t will be to you . Of the: 70 ce~cs ~ 27 , ... ere ma1es, 37 were fem.lles

and the sex of 6 was not stated. As it mekes a good deal of d ifference qt

what age the tumo rs devel oped , I have divided t he ch ildren into quinquennfa.

f rcm 0 .. 5 years there we r e 27; f rom 6 .. JQ years there '"er~ l8 , and fr.om

11-15 years there \<~ere 25. Al together there were met astases in i4 which

Case 10. (cont1d)

is 2~. If we take only the younger ~hi l dren in the first two quinquennla ,

there were 45 cases with metastases in 8 which is 17.5%. It is therefore.

quite ev ident that thes~ tumors can metas tas ize . But I t Is Impor tant to

note th~t in on ly two cases was t he tumor known to be fatal and the

~tastascs were found at ~utopsy; in one in the liver. coming from th~

gluteal r~gion; this was In • 3 year old child and in the other in the

lung 15 years aft er a tumor had been removed from the ear of a 15 year

old girl . Of the 70 turnor5 33 were in the extremities with metastases in

7; 28 were in the head ardnoek reg ion .,, i th ffi(: t as t ases In 4; 7 were in

the torso wi th me tast ases in 3 and tho pr imary site of two was not stated.

Thoso figures regard ing metastoses a re onty of relative value for in most

of the other '-ases we do not have any fol k1..,-up.

With a reeord such as this I would agree that ft is of little

importance to remove the regional lymph nodes of ch11dren with melancmas

bcc~usc even if t hey s hou l d prove later to have regional lymph node

metastases they can be removed at~ subsequent operation ~ppa rcnt l y wi th

very sl ight danger of further spread. HOI. ... ~ver , when one Js dea l ing with

p i ~e.nted tumors beyond the age of IS yc_ars , I confess that I am unable to

recognize a so-called juvenile melanoma in an adult and I apply in each

c4se the c~iteria by which I try to dete~ine mallgn4ncy: (I) invasion of

the epidermis so that viable mclanoblasts can be found In the kera t inized

layer of t he epidermis and (2) ce llu la r cha rac ter i stics of malignancy in

the tumor cells . If e r the r one or both are present ln t he tumor of a patient

past the age of 15 years, I judge the tumor to be truly ~l lgnant . There are

those who believe that they can teeognize juvenile melanomas in adults;

peth4ps they can but I cannot and I am afraid to try.

Case 10. (cont ' d)

may say thot in rega rd to this S~in~r case, I am unable to

recognize evidence of ma lign~ncy in it. presume I t ls what L~urcn

would call an epithelioid ce ll naevus. tty objecti on to the use of thi s

tenn and the other term for benign naevi that Imitate mnlf gnant tumors,

namely spindle ce l l naevi , is that this d iagnosis depends entire ly upon

the size of the nucleoli In the c~l ls which is a pretty tenuous criterion.

I find it ve ry dif ficu lt to se lect a sat isfactory name fOr possib ly mal­

ignant melanoblasti c tumors in chi ldren. Juvenf1e me,lanoma ·..rou ld be very

sati s factory were It not for the fact that thi s term has been used not

only for tumors in children but a l so for t umo r·s in Ddults. am f orced

therefore to use some oth~r te~ such as ~llgnant mcl ano~~, juvenile t ype,

ju~cni l e pigmented mol ~ or n~evus or sooe ot~er equally oOjectlonable t~nm.

Because It docs have a very low potential of mal ignancy I feel compe l led

still to use the tenn juvenil e malignant melanom.1 .

I agree t hat in dd ldr'cn tr,e cha nces that a melanoblas t ic tumor

wi ll serious ly threlten l ife are so remote that would not advoca te

regional node dissection as a r'Outine procedure in children.

Case 10 . (cont'd)

Raference1 .

Hcndrix , R.C. Juvenile mel anomas. beni9n and ~llgnant . A.K.A .Arch.Pa th . SS: 636- 644: 1954.

Kernen,J.A. and Ackerman,L.V. Spind l~ cell nevi and epithelio id cell nevi (so-coiled juvenile melanomas) in chi ld ren and adu lts. Cancer 13:612- 625: 1960.

HcGovern,V.J. and Goulston,E . Feb. 9 , pp,ISI- 182:

~a lignant moles In childhood. 1963.

Med.J .Austrol.

McWhortor,H. E. and Woolner,L.B. Pigmented nevr. Juvenile me lanomas and ma li gnant melanomas In children. Conc~r 7:564-585: 1954.

Myhre,£. Ko ll gnant melanomas in children. Acta P~th. e t "icrobiol. Scand. 59: 18~-188: 1963.

Russo,P . E. Malignant melanoma in infancy . Report of three cases. Radiology 48: 15-19: 1947. (one congenital)

Sweet , l . K. and Conncrty , H. V. Congenital melanoma: Report of a case in which antenatal metastasis occurred. Am:J .Ois .Chlld . 62:1029: 1941.

Truax,K.F. and Page,H.G. Prepubertal mal ignant motano~ . Ann .Surg. 137:255-260: 1953.

Wi11iams,H.F. Melanoma with fatal metas tasis in Si-ycar o ld girl . Cancer 7:163-167: 1954.

•

Case 11. (P&S 78063)

Microscopic. This tumor of the brain in a chi ld seems very con­

fusing to a person such as I am ..,Jho seldom sees brain tumors either in

adul ts or children. note that there is a good deal of. fibroblastic

tissue all through the tur.~r which Is unusual for mos t glial tumors. Yet

the small rounded cells caught in the fibrob lastic network look a gqod deal

1 ike glial cells. Fortunately some of the pieces of tis.sue show a picture

in which the cells ~re larger, fatter and sometimes arranged in definite

C?r' suggestive \othor ls. Th is is a picture of meningioti'ID and on the strength

of this finding I assume that this tumor is a menfngioma.

Discussion. This tumor was regarded by Kernohan as an atypical

meni ngioma. It has se~ed to me that the tumors of the nervous system,

especially the central nervous system have svffered too much from in­

vestigation by specialists who have not h~d suffieient experience vJith

the behavior of tissues and tumors arising in other p~tts of the body .

The history of the study of nervous system tumots Is int~resting . I t \·1as

first undertaken by general pathologfsts v1ho had only a secondary interes t

in the nervous system. They made a sorry shcx.<~ing . h then was taken up by

the Spanish School and continued by the neuroputhologist.s who "'ere influenced

by the Spaniards and lat.er continued by Cushing and the brrltiant young men

.,..,ho grew up under his influence. ttost of these men, hB\1 ever_, were not

primarily pathologists but neurosurgeons and they had too l i ttle experience

with the res·t of the body. Consequently the nervous system tumors are no""

so loaded wi.th mult iple t erms tha t it ts extr emely dif ficu lt for anybody

to gain a clear conception of t he ir behavior. I thi~k Kernahan while a

ncuropath~logist primarily has been most of his life in elose contact w1th

t he surgical pathologists at the Mayo ClJnlc and h~ has a better conception

Case I I , (eont 'd)

of the relationship of the nervous system tumors to those in the rest

of the body as hi s book on SarGomas of the Brain shows.

Reference .

Kernohan,J.W. and Ulhlein,A. Sarcomas of the. Br:dn. C.C.Thomas, 1962 pp.l-192.

•

Case 12. (P6S 78601)

Microscop ic . This tumor of the l iver appea rs tom& to be compos ed

of many cords of rqther imrnllturo I iver cel ls wi thou t any bi l e duct epi­

thelium or Kupfer cel ls. Separat ing the liver ce l l cords are masses of

fibroblast ic ti s sue composed of rather small oat-shaped fib roblasts t hat

are comp l etely surrounded by very fine reticul in fibers m.king a finm

mesh. A third el~nt consists of bal l s and rods of dense collagen with

the arrangement of cancellous bone or osteoid . It is que1tlonable, h~

ever, whether I t 1s reall y osteofd because t here are se l dom any lacunae

wlfh ce ll s In them. The ma rrow spaces have large cell s that might be os teo­

blastsi tn any event they d iffer from the fibroblasts and the I iver cel ls.

There are no reti~ull n fibers rn the apparent marrow spaces . If there are

any mltos~s I have not succeed~d In finding them.

Discussion . A n~ber of cases of congenital Mixed tu~rs of the

l iver enti rely c~parable to this one have been reported. I t is qu i te

reroork.able how clo~el y the histologica l pictures resemb le one ano ther.

Most autho rs have as sumed thot the balls of appa~ent osteo id ~rc real ly

bone although there Is no bone marrow. Since sometimes the tumor has gri t ty

areas there Rust be at least calcification. The liver cells 4nd the

embryona! fibroblaStic tissue •ret the scoe in all. Var-iations noted in

occastonal cases are the formation of t rue bone and cartllage , squamous

metap lasia, occas iona l bi l ia ry tubular e l~ents . Some DUthors d~sc r i be

plent i ful mi toses and c~nsider the i r tumors ma l ignant but appa rent ly they

do not metastasi ze . The question of whether or not these tumors are com·

parable to \rli 1ms1 tuoor of tho kidney is discussed by All I son and Wi 11 is .

There are dlfferenees for \1( lms' turi.ors holrdly ever form bone: or ccuti I age

and frequently fonm rhabdomyoblaltfc tissue wh i le the reverse Is true of

7

•

Case 12, (cont'd)

the liver tumors . Further. Wilms' tumors a re defi nitely mal ignant tumors

wh i le it is ques ti o~able whether or not theso lfver tumors c~n be so con-

sidered. Tumors somewhat comparable to those fn infants <lre occ~slonally

observed In adults (Barnett et al) .

The p referr-ed term for tumors of thi-s sort is mlx.c.d tumor. That

s eems acceptable to me. It differs from the tera t oma and the- pure carcinomas

and therefore needs a different name.. I f the ml.xed tumor of' t he liver ever

m.etilstasizes it must be -a very rare event for fn a l'athcr hasty teview of

-t'eportod cases I did not find any examples . It w-ould se4!m therefore that

this infan t should have an excellent chance.of cu.re since he has survived

a right hepatic lobect omy .

Re:fe renee .

Allison,R.M. and Wfl l fs,R.A. An ossifying embryonic mixed t umor of an Infant' s liver. J . Pa th.& Bact. 72:155-159: 1956.

Barnett,W.H., Erickson,E. E. and Halpert,B. Embryonic tumors of t he 1 ivfr in on adult . Cancer 11:306-309: 1958,

Edmondson,H.A. Tumors of the At la·s of Tumor Path. Hepatic mixed tumor .

1 iver and intrahepatic b fl e duc::ts. Section V! l, fascicle 25, AFIP 1958. pp.l52-158. .

Pang,Shu-C~ao"'" (~1 11 fan S.C .Pang) &ony a ad' cart: laginous hcpa rtoblastom<l. J. ~o th,& sact. 82:273- 280: 196r .