Thymoma Anemia Refrakter

B L Q Q ID The Journal of Hematology

OCTOBER, 1954 VOL. IX, NO. 10

The Simultaneous Occurrence of Benign Thymotna and

Refractory Anemia

By JosEPh F. Ross, STrAJLT C. Fixcit, RUSSELL B. STREET, .Jn. AND

Joux W. STRIEDER

T HE PRESENCE of a benign thymoma and of a refractory anemia which

failed to respond to all therapeutic measures has recently been observed in

our clinic in two patients. rfhe simultaneous occurrence of two unusual pathologic

states in two patients within a relatively brief period of time suggests a probable

relationship between the thymic tumor and the erythropoietic abnormality, a

probability which is strengthened by the finding of reports of seven similar

eases. This unusual coincidence of abnormalities in the thymus and the blood

provides one more link to the legendary (and frequently nebulous) chain of

evidence connecting the thymus gland with the hematopoietic system. We report

herewith the clinical, hematologic and morphologic details of our patients with a

summary of the previously reported cases.

CASE REPORTS

Case No. 1

12. IL. , a 44 year 01(1, single, white fenntle housekeeper, eight years ago ( 1945) was found

to have an anterior mediastinal maSS by survey x-ray examination 51w was com�)letely

asymptematic at that tinw, onid refused surgical exploration Three years later (194$)

numerous, severe, intern�ittent frontal headaches appeTtre(l, afl(i she �s’�ts found to he mark-

edly anemic by her local physician \Veolkness, 1)all)itation, and (l�\-spneoL appeared, and she

was hospitalized at a local hospital where she received several transfusions of whole blood.

The followi’�g month she ��‘as again hospitalized for investigation of her anemia and for

transfusions. Bone marrow aspiration biopsy showed a decreased number of erythropoietic

elements, normal granulocytopoietic elements, and a generalized increase in large, multi-

nucleated cells which were suggestive of Heed-Sternberg cells, An axillary lymph node

biopsy was negative, hut on the basis of the multinucleated cells in the hone marrow it was

felt that she prol)al)ly had Hodgkin’s disease. One month later symptoms of alleflhia again

recurred, and she was admitted to the Massachusetts Memorial Hospitals. Careful inquiry

at that time failed to elicit a history of exposure to any benzol derivatives or to other sub-

stances known or suspected to impair hematopoietic function. Past history and family

history were essentially negative Physical examination revealed a pale, well nourished

female without visible icterus. The supraclavicular and axillary lymph nodes were palpable,

averaging 1 to 2 cm. in diameter; they were freely moval)le and nontender. There was an

From the Robert Dawson Evans Memorial, the Departments of Pathology and Thoracic

Surgery, Massachusetts Memorial Hospitals and the Departments of Medicine, Pathology

arid Surgery, Boston University School of Medicine, Boston, Mass.

Submitted January 18, 1954; accepted for publication February 8, 1954.

This work was supported in part by a contract between the Atomic Energy Commission

and the Massachusetts Memorial Hospitals.

935

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L.L. I2-3�,�q J i

l’u;. I . --l1ostel’oalit etiot’ :11111 left lat eral x-rays of (‘hiest on pat ietit L. L. , showing well

l’il’(’tllilS(’l’ill(’(I atit(’riot’ lii(’lhi:Ist 111:1! 1 utlillI’ l)l’�j(’(’l jug jilt II left lung 11(111.

936 1)I�XIEN TlIY\lOM� \VITII ltEFlto(”f()HY �NEMl.�

I1(L Of l)1d’(’�I(liTIl IItlllII(&iS i 11 1 lie tll)l)eI alit Pliot (‘best , (OXt PtI(li tig 6 1 (1 5 eta .I o t he l(ft ol t he

IiSi(lst cn-nal li ne ;\. grade I I al)i(-al syst olic nisuinnur �sas l)1es(OIit ‘FIle liven e(lge V�:IS I(�1t 1

I 0 2 ens I telo�v t he right (-ost a! in�s rgi n a tid t he t i J) of t he spleeti � � ‘� 1 �:I ble a t t he left

(‘1)51 al nialgi ii on (led) i I1SI)i tat i oil.

L(ll)Ot(ZIOI!/ (1(1(0: t’rinalvsis �tss ncgat ivc Px(’ept for a 1 4- tihunsi ii i ii t � of six specimens.

rFlIe lIiiit ott test! lot S\’l)IIiIiS ��.tIs negative The l’e(l blood (-ount �vas I .6 nsillion1’cu. 111155

liPIlITIt ()(‘I’it 141) I)(’r ((‘lit . henIoglol)in 4.8 (mi. pet’ (‘ent , MCV 87 (‘U. j�. M( ‘11 30 �g. . MCHC34.3 J)(’l’ (‘(lit , �vIiite blood (‘OUJI) 21(X) pcI (‘U. itil. �vitli a (lifl(’l(’lItial of 53 11(1 (‘PIlt lU)lVIflI)I’-

I )lH)llUC Icai’ leukO(’\t (‘5 , 4 pet’ (‘cOt I )TLIIEI foi’ins, S pet’ (-cut lynsploicyt es, 1 � �‘(-emit nl000(’vt PS,

(11(1 4 per (‘(‘1St (OSiIU)J)hilS . The met icUlo(’yt P (‘oulit \VTIS 0. 1 I)e1’ (-PItt �1tI(l t lie Coomhs I (‘St

\�:is tiegat ive , The \Vi ii t I’I)I)e se(Iinl(’nt at ion oat e �ots 1 6 inns . /Iim. ( coiled ed ) , ‘The I)lTtt (‘let

(‘I)UItt \\15 I 13,(XX)/’U . 111151 .( 1((’eS-l’A’ket’ I11(’t 110(1) “1’I#{236}eictetic i 1i(leX was 6 tinit-i. rflle 11011-

1)1(11 Cl 0 nit �‘ogcii �T1S 22 issg. pet’ c(’Ilt ; t he t ot ttl protein 5.06 (illS. l��’” (‘(‘lit wit Ii an a11�unuiiof 2.5$ ( iss . pet’ (‘(‘lit . �\.l kali ne PliosPhat a.se �vas 5.02 i�odaiisky UOi t s. ‘fli lee 1)10(1(1 (‘lilt Ul’d’S

111(1 fiv(’ stool guaia(’ 1 est s were tiegat ive. Chest x-ray (fig. 1) revealed I lie pl’eselice of a

��el 1-ci t’cumsc Ii l)e(I mass measuri tig al lout 8 (‘�. ill (liamet (‘1’ 111 1 lie alit (‘liol’ mel ii ast ilium

wit Ii its ul)l)(’l’ surface at I lie level of t he sI el’liomaliUhl’ial j Illi(’t loll. lliis I11�SS J)l’Oj(’(’t e(l

i lit 0 t lie left milisIle lung field. The :1011 ic aN-li (li(l not appear to be i tivol veIl. The appeal’-

atice stf I his mass suggest e(l that it was ei I hel’ a (lermoi(l (‘ySt sIr a I (‘rat 0111:1

(‘I,,,, (‘(ii (‘011 ise: Ihe pat ietit again was t ralisfuse(l to a normal level III (‘1 r(’ulat i ng ei’vt is-

rod-v I (‘5. 1 lowever, in less t han :1 IflI)Iit hi S\’llll)t oms 1)1 anemia recurre(l , a 11(1 she was read -

mitt ed to I li(’ hiospit :11 ill Novemh(’l’ 1948 At this I ime this’ only (‘halige iii physical findings

was an elilargemelIt of t 1a’ spleell \VlIi(’hi was PI1Pa1)le 4 cm. 1lelow t he left cost :tl ma rgi 11,

I ala)l’at oi’\’ st I1(lies agai Ii revealed a 1l’Ofoulid anemia wit Ii 0 pel’ cell) i’s-f i(’UlO(’Vt (‘S :111(1

severe I hroml los-vt Ol)eliia. The (‘ooml )5 test wa� posit iV(’ oil three sellarat 5’ occasiolis, a 1111

lieu’ was mo(lerat 5’ (‘1ev:)) ioli (If I lid’ serum hili i’uh,i Ii. The eryt hrocvt e osmot 11’ fragility

was normal , I lut :�shi 1�v I ransf usi oti survival sI udies showed a rate (If tell cell dest ruct ion

whi(’h was tist’es’ t iIll(’S liormal . * It was apparent that an :icqui red I ype (If hiemol I ic anemia

was l)res(’lit , 111(1 that 1 his cllmplicat ion coupled wit hi the (lee l’easell l’:it (‘ (If (‘I’yt hll’lIlIoieSiS

hi Till pl :I(’(’( I t hI’ l ):Lt i (‘lit 111 Ti �l’TI ��(‘ (‘Oh (lit 1)11 .Beca use (If t hid’ hIeIllolV t i (‘ TI tiemi Ti , spletiec t omv

* _\ shh �v di f1’el’elit i :11 agglut i nat i (Ill st udies :111(1 (‘ootiii �s t est 5 W(’l’(’ p(’ if (II’mel I I �v 1) r.

Charles P. LIllet’S(Ili - 15) \\iillIli we eXpl’ess our appre(-iat illll




115)55, FIN(’l I, STREET, .\ND STill EDEE 937

was performed! December 15, 1948 without ill effect. The spleeti weighed 450 Gm. and showed

(‘ongestive changes characteristic of hemolvtic anemia, hut no other abnormality, Follow-

big this the Coombs test became negative (January 13, 1949); the rate of erythrocyte de-

struction returned to normal; and the red cell survival, by I lie Ashbv te(’hini(’, was normal

on March 15, 1949. The platelet and leukocyte counts which had been low ret urne(1 to nor-

mal following splenectomy and have remained SO sihlc(’.

She failed to show an�’ evislence of red cell forniat ion :111(1 one months later �s’as again

Fio. 2-llist ologic sect ion of bone marrow from (‘as(’ no. 1. The marrow is cellular;nsveloid elements and megakarvocvt (‘S are l)resent - but ervt hroevt e Precursors are absent

(X 850).

FIG. 3,-Stained hone marrow aspi rat ion smear from case 115). 1 , demonsi rat big t he ab-

sence of ervthroid elements IX 972).




Fl ( , 4 -GlOSS �l)II�� 1:115cc (If 1 hiytiiis’ I umsll’ fl’l Ins (‘TI’S III 1. 1

938 l1l-�NI(iN T!IV\1O\IA \\i’fll IlI’FiL�(’i’�)ll’i’ .�xl;Ml.\

hiospil :lliZ(’d fot’ :oldi I iohial I l’ahisfusi(Ilis. ile �lhiy5i(’al ex:ttiu ha) 11111 \�T15 (‘Ss(’hIt ially un-

chiahlged , :111(1 1 lie (Ilil\ sighil fb’atit s-h:usge i Is lahot’at ot’\ 11:11 a \�TIS a ‘el situ of’ I lie 111:11 clef

count t (I li(Ilflia I , slight leukocvt osis, liegat i ye (�ooIniIs I s-st . a Ill I I .isal)l)eal’ahi(-(’ of t lie

I li li huh Ii tiensia . lli’ fout’t Ii bosjlita I :I(llfliSsiOhi \‘TIS I hi-ce mont his l:tt ct, a I which I i me a secon(l

51 el’llal I ‘one Issa h’l’(I\’ aspi t’:tt i oIl ��as l)cl’f�1nie(I . \‘i t’t ually till eryt hi I’ll! I I elenien t s \\(‘re pIes-

(‘lit , hlut t hel’(’ \VL5 (‘vi (1(91(1’ (If vet’v act ive gl’ahiulocvt olloiesis ( figs . 2 a till 3 ) .F�Illo�vi ng 151(110

t lahisfusi (1115 , agai n she ta pi(ilv because :stiensb- , :111(1 \\Ti5 l’ea(lnii I I II I I o ) Ise hlosjli t :t�l uric

1110111 Ii lat (‘I’ . The 51 (‘ I’ll:) I 1llIli� tiiTLl’l’OVo agai Ii \�as (‘XTttiii hell a tu 1 �‘:IS tills’ ha �ige� I . \Vi I hi I he

lloj)(’ t hat ‘ensoval of t lie nselhi:Lst inal I unstIl’ tiiiglit iIiiJll’llv(’ l’tyt hlt’lllloiet il 11111-I ioli , (In

i�I:t� 23 , I 949 a bIns . ehicTlh)sulTtt ((1 1 1111101’, U 11Th 1 a(’hse(l I o Sut’l’(Iulll hi tig st l’u(-) ul’(’s, \�:1s ic-

Inovet I fl’lIns I Ise left 111)1 I(’l’ alit cli (II’ 1’lie(hiTIst i 1111115 . ( ) Ii glOss I lisl)(’(’ � i � III I hu UltIOl’ TI Pl)�a l’(’(I

aS a (-olnplet ely ehi(’TIh)slllTlt elI , flat I cued, oval 155:155, nieasut’itig I I )< 8.5 X :1.5 � . ahill �veighi -i rig I 71) ( iii .� This’ ext eli 01’ sut’f’:ice ��as pi nkish -gl’ay t 0 r(’(l \Vi I hi tiunset’ous ailhiesi v(’ I :11)5.

Tisete �:ts slight Illhulat bIll :111(1 1 ha’ niass \\.:IS fi tIn I o Pall)at 1(111 1 fig. 4 ) . �fhe (-lit sui’f:tce

l-evealell (l(’el) vellowishs-hl’owli lobules vat’vi rig tom 0.2 cm. 111 2.1) cm. ill diatisst el, sepa -rated frI IriS ea(’ Ii ot his-t’ Ilv Ii I 11(1115 tissue hatids. A small a lea of su II(-aI Isul :11’ hemorrhage was

pl’esehi I at Oti(’ 1)11 IcOn lust ologic exami 11:11 1011 t Ia- 1 umol’ was s-oml)lIse(l (If I wo types of (‘ells. ( )tie type TIp-

Pealed 1(1 lIe idehut b-al wit Ii a�i adult lvmphiocvt e. It o(-(-urt’e(l its souse areas as laI’ge sh-et s

of Uhii form (-(‘1 ls wit bout (‘vi(leli(’e of follicle format ion - 01’ a(lmi xe� 1 wit Ii I hse second t vpe

cell, t he sIll hilIle (‘eli. Mit d)5(’S ws’t-(’ 11(11 appal’etit :111(1 si lvi’ st ai tis revealed o�i ly sI-alit he) ic -

ulum fil Id’s among I he lvmphocyt e I �‘pe sells. The sIll n(Ile (-ells (I(’(-ulre(l ill ut et’laci tig

whorls, (If tell hi nell Up ill parallel fashion - giving a pahisa(le(l apllearahi(’s- 01 101-mi rig pseudo-

rose) t(’s :tI lout small Illood vessels. Ill Some al’eas t hiese spi Ill Ile cells formed dense s-s’l 1111:11’

masses wit hi (Ill ly o(-casi sInaI scat t (-led lvniphiocyt es (fig. 5) . Ill 511 hiet’ a I’s-as I i hiV \V 110115 III’

pseuslol’oss’t Is-s of spi n(Ile cells o(-(-uIIesl i lucohispi(’uously among Ia l’gs’ sheet s of lymphuocyl es(fig. 6 ( . ihe spindle sell nuclei wel’e f’a�i t-l�’ uluifol-m wit hi fihielv slivillesl - Iighst ly st ai tii ng s’hro-

151:1) ill, and wit hiout hiucleoli . Neil lid’ mit oses 1101’ gi alit t umol- s-el Is wel’e a�)pars’hit - :111(1 1 lie

s’vt oplasm was i lIslist i hu(’t :111(1 eosi tiophi lid’. Thuele was rio collagehu s’xs’eI)t in I lie dense fil �t’o-

s’ollagenous sept ae whi(-hu ss’parat e(l t lie ht’oad sheet s of I umot’. Si I ye!’ st ai us revealed deli -

sat s’ let is-uluni fills-I’s surl’oulush tug small gt-oups of s1lllu(Ik’ cells. F’i I ll’� Is �\ele tu(It sieniotu -

* This 111151111’ hl:l�s Ileeli descl’ihlelh by Pope :111(1 Osgood’ as case till. 3 in their set’i�’s.




11US$, FIX(’Il, STREET, ,�XD ST1IIEDEII

FIl. 5.-Histologic sect ion of tumor from case no, 1, i llust rat i rig a palisalli lug (If spi tudle

cells tetuding to pseud�roset t e format ion :lIsd a few s(’at t eresl lymphuos-yt s’s I X $50)

FIG - 6.-Histologic see t i on of I umor frons sass’ riO, 1 taken from an a rca ��hue l’s’ I his’ sla lull he

cells occur iluconspid-uously atiis��ug large sheets of lymphocytes ( X 6(X)).

st rable in the s’eriters of the rs)set te-like st rust ures. The cells lli(1 luot appeal’ ams’Iloid 1101’

(lid they exhibit cytopluagocytosis. Hassel’s corpuscles were hot seetu,

The surgical removal of t his t umor failesl to ilufluelus-o’ I hue rate of cry) hI-sb-Vt e fol’mat ion -

and during the ensuing year at intervals of about six weeks she was admit) ed for t ransfu-

sions of from 4 to 6 units of red (‘ells. I)urilug this periosl of time she was givs’lI 1:11-ge shoses

of Valentine’s liver extract, of papaitu digest of liver, of ferrous sulfate, fohic acisl, :111(1 (‘5)-

baltous chloride (all by nsout hi) and of s’rude :uud refined livet- ext ract :11111 (If vi I ansi Ii B12




940 BENIGN TI! YMOMA WITH REFRACTORY ANEMIA

by injection-all without demonstrable beneficial effect. In July 1950, 80 tng. of ACTH was

administered intramuscularly daily for six days, and in December 1951 she was given 100

mg. of cortisone daily for fifty-two days. Neither of these substances stimulated erythro-

cyte production and anemia recurred at its customary rate. During the past three years

she has continued to receive many transfusions, and her skin has gradually developed a

deep grayish-brown cast, especially over the hand, forearms, and face. The plasma iron

binding protein is com�)letely saturated with iron. Polyuria, nocturia and glucosuria have

appeared, the glucose tolerance test is typically diabetic, and insulin therapy is now neces-

5T1 ry.

This patient now has had thirty-nine hospital admissions during the past five years and

has received a total of 174 units of red cells. This represents about 40 Gm. of iron. Three

additiotial I)one marrow examinations have revealed no essential change except for pro-

gressive increase in amounts of marrow hemosiderin.

Eight months ago (April 1952) the Ashbv transfusions survival study was repeated and

indicated a normal ervthrocvte survival. At that same time studies employing the radio-

isotope Fe59 showed a 9.9 hour 50 pe� cent plasma disappearance time of Fe59 with less than

1 per cent of the injected radioiron appearing in the circulating red blood cells three weeks

after the time of administrations.

Summary: A 44 year old single white woman in whom an asymptomatic sub-

sternal tumor was first demonstrated eight years ago. Five years ago a severe

anemia developed and the bone marrow showed a marked decrease in erythro-

poietic elements. An acquired type of hemolytic anemia appeared and was re-

lieved by removal of the spleen which revealed only congestive change. The

hypoplastic erythropoietic marrow and severe anemia persisted. Four and a half

years ago the mediastinal tumor was removed and proved to be a thymoma,

but this did not result in any relief of the anemia. Treatment with all known

hematopoietic agents as well as with ACTH and cortisone did not benefit the

anemia which is controlled only with blood transfusions, one hundred and seventy

four of which have been given to date. As a consequence of the transfusions,

signs of transfusion hemochromatosis have appeared and severe diabetes mellitus

has developed.

Case No. 2

E. T., a 45 year old, white housewife, was admitted to the Massachusetts Memorial Hos-

pitals two years ago (May 1951) complaining of a dry cough, weakness, and a mass iii the

left chest. Two months before admission she developed a dry, nonproductive cough, weak-

ness, and slight fever. She was found to be anemic with a hemoglobin of 3.6 Gm. per cent,

and was hospitalized at her local hospital for transfusion therapy. Two weeks before ad-

mission she developed dull, aching left chest pain and recurrence of her anemia and was

again hospitalized and transfused, Chest x-ray at that time revealed the presence of a welldefined tumor mass situated! on the anterior aspect of the left side of the heart, and she was

then transferred to the Massachusetts Memorial Hospitals for surgery. There was no his-

tory of exposure to benzol or to other agents known or suspected of being toxic to the bone

marrow. Past history, system review, and family history were noncontributory. Physical

examinatioti revealed a cooperative, intelligent, pale female in iso acute distress. The skin

was not remarkable except for pallor. There were two firm, nontender, movable lymph

nodes 1 and 3 cm. in diameter in the left axilla. The chest showed dullness to percussion

with absent breath sounds over the left lower thorax anteriorly and below the level of the

seventh rib posteriorly. The heart was not remarkable. The liver edge was palpable 4 cm.

below the right costal margin in the midclavicular line. The spleen was not palpable and! the

neurologic examination was negative.

Laboratory findings: Urinalysis negative, Hinton negative, red blood count 3.55 million/

cu. ml., hematocrit 31.0 per cent, hemoglobin 10.8 Gm. per cent, MCV 87.2 cu. �, MCH 30.8




ROSS, FINCh, STREET, AND ST1IIEDER 9-11

* This tumor has previously heels described by Pope and (isgood1 atsd is their case no. 7.

FliT. 7.-Postel’oaritel’iot’ alill left lateral x-t’a\’s d)f shiest on 11:11 is-lit I’ . ‘IT. Thus- P05I (rI)-

atuteriol- X-1a\’ \VTIS niade aftel’ I hiot’as’etut esis hu:sd Ileelu IIel’fot’tiselh a tish 11)01) cc . of flui I I t’e -

nioved, ahisi t here is collapse of t lie left lowel’ lobe.

� NICHC 34.9 ps’� cent . Tue l’etis’ulocyte count 0.3 I)5’I’ (‘(‘lit , II1II5’l(’t (‘(lull) 25$,()tX)s-tu.

miss. and white blood count 10,450/cu. inns. with :t dliffen’ehstial of 73 I)(t’ (‘elit lila) tue gl’anulo-

cytes, 17 l)s’� cent lynsphos�’t es, 6 per remit nss)huos’ytes :115(1 4 I)(h’ s’elut eo5i lllll)Iui ls . \Vi lit h’oI)e

ervthrocyte sedimentation rate 34 inni./hir. (corrected) , alud thse is-Is’l’ic ilidex 7.5 utuits.

The Coombs test was negative alud fecal urobilihsogelu excret iohu was 1501155:11 , ( )t Iis-t’ St ulli(-s

revealed a tionprotein nitrogen of 24 (.Ini. per cs’nt , total p1’s)teils of 6.48 Gtn. 1151’ -etit , s(-rum

alh�unsits of 3.58 Gm. per cent , ahssi total bilirubits of 0,3 nig. p�’� edit . (‘huest X-l’aV l’eveale(l

the presence of a large, well defines! tunsot’ niass itu the aiutei-ior nsesliastiluuni I fig. 7 ) , The

left lower lobe was atelectatic, flubh WaS present , amid there ��‘:ts o’xlellsive (‘als’ifis-at ion of

the i)ar:ttracheal lyniph tis)(les. (hue t housarud cc. of st raw coloted fluid l’emovs’sl ft’om t lie

left chest contained large numbers of lymphocytes, hut was negative for tumot’ cells. 81cr-

nal marrow’ aspiration demonstrated marks’s! Isyperplasia (If t lie g1aluulos’yt ic S(’ris’s. -hiefly

of the mature polymorphonuclear leukoeyles and nsetamyelocytes (figs. S :511(1 #{182}H.1’t’�’t hiroill

elenieusts were greatly slecreasesl ihi huumhel’, hut :1 few red cell Ilrs’s’tlrsl)l’s wIle Ilr(’serit

Granulocytic elenseruts and megakaryocytes wet-c normal. Thud-I’d’ was a slight ilicreas5’ ill

plasma cells. Left axillarv lymph node biopsy ievealesl Isormal lynsphi luolle all-ho Is-s-I ul’e,

and ItO evidence of tumor.

Clinical course: Upon the s-ompletion of these stushies it was felt t hat this- pat ietit probably

had a malignant chest I union’. Followihug a negative hlronchioscopy atu exlllot’at s�ry t hsora-

cotomy was performed otu May 22, 1951. A spherical, tuohul)es!unculatell, tumlIl’ masS, lying

ant el’ior :111(1 lat eral to) t lie base of the I)erica l’lli um, was removeol froni I his- lIft :ttit s’rislr

medliasti num wit hout adverse sequelae,

On gross inspect i Oh t he speci meti s’ohusist NI of a sensiencapsulatell I urisslt’ tiueastu ii rig 10 X

9.5 X 6.5 cm. and weighing 270 Gm.* Thus’ exterisal surface was pinkishu-gt’a�. firm, :11111 COhU-

posed of whorls ansI lobules with ihuterlacing, fitie, gra�’-whuite fihl’ous s) 1:111115 1 fig. 10).

histologic examihiatioli revealesl :1 t umot’ composesl (If t lie satiie t \VO I YI��’� (If cell sIc-

scribed in the previous case. This’ masses (If cells were divided into) large, il’rl-gulal’ lslhlules

by dense fibrocollagenous h)ahsds, This’ spilsdle cells slid tuot fol’m laI’ge solid masss’s IS ill this’

previous case, but were scat tered uhuifornily amid ilicoluspicuous!v amotig I hue lvtusphiocytic




942 BENIGN TI IYMOMA WITh IIEFRA(’TORY ANEMIA

F’i s;. S. -Histologic sect �dIri of hone tuarrow from (-ass’ rio. 2. Grariulocytopois’sis is active,

megakaryocyl es are nuunserous, Ilut el’yt hurs)I)oietic activity is gt-s’at lv rs’dus’s’sI (X 600).

Fl s;. U --SI ai tied hotie marrow smear from -ase no, 2. No) ervt Ii ron d s’lems’tu Is :t rs’ ��s’Ss’ll t

(X 972).

sells. in soms’ :(l’eas, however, thus’s’ tehlded to group togethel us small nests, sometimes pali-

sallell or whol’hs’sl (fig, 11); ill (It her :sreas t hss’�’ formedl rosette-like st ruct ures (fig. 12) , Fibrils

were riolt demolist rable in t lie i’oset Ic-like areas. Collagen olepositis)n was inconspicuous,

ret iculuni libel’s were scat tored I hsroughout and only occasionally slid t hey sul-rounud small

groups (If sPlhs 01 itsslivishuah sells. Hassel ‘s corpuscles \\‘s’l’s’ hot aIlI):irent




.� ‘SFm�. 10.--G ross appeara�ice of t umor removed from (‘:1St’ tob

BOsS, FIXCII, STREET, AND STII1EDER 943

Following t he opd’rat iO)hi five Uhlits of rest o’el is were mImi hlistehesl alidI I hue ha’tui:t t Is Ii t was

elevated t o 42 pcI’ (‘chit . She was ohisshal’ged 011 1 lie t �ve1ut is-I Ii llay free f’I’lbns sytui�lt suns.

One nsonth after discharge she was again reaslnsitts’sl to this’ ius’slical servicl’ l’oniplaihuing

of weakness, I)rodlus’t i ye cough , ahiol heaslachue of t en lI:IyS olurat ion . The I)OSi � � � I )hysica I

findings o’onsisted of nioderate pallor of this’ skin ansI a healed left posterior I hloracio’ soar.

Physical finohings i ii t he left chs’st were hiornial . Laborat or�’ olat a shullwsll a 1101111:1 1 un tue,

red blood coutst of 2.9 milliomu/cu. mm., hiematocrit 19 pcI’ cent , ansI hiemoglohlili (If 6.2 (tuu.

l)C� cent . Platelets were 265,0(X)/cu. nins. and white hlooal couiut was 67()0 �‘u, 11111). wit hi :1

tiornial differential . There � free hvdlroo’hiloric acidl i Ii t his’ 51 oniachu . Si x utli ) s of red (-(‘115

were adiministered between Septeniber 22, 1951 ansI Novs’niber 15, 1951 :uull hue huematoo-rit

rose t o 45 �er cent . Ati AshiI�’ differetut ial :tggluti nat iotu st udy i 1u(Iis’at esl a tus�t’zsia 1 survival

of transfused (‘ells. Two moIst Its later she was again I ralusfused wit hi elevat iou of hemat o-

erit from 19.5 to 46.0 �er (‘elut . She was then given 100 nig. of cortisohie slaily for a period

of fifty-six days wit hout deniolist rabls’ effect iii ao’s’elerat i rig eryt lu rocyt e p110 luct i s)tu. She

also w’as given crude ahidi refiuued liver ext rad-t :uud vitamin B12 by inujes’t iotu - :11111 folio’ :11-ill,

crude liver extract, ansi s-obalt ous chloride by iiiout 11 �vi I hout hettefit

During the past two years she has continues! to) r(’slui re regular I ralisfusil)11 his’rapv for

hier anemia and has failed to show’ any evidence of ervt hiros-vte prooluct ion. No ahbluornial-

ities of leukocytes or platelets have bs’en obss’rveol. I)uring tluis ps’rio)(! she hi:ts rs’o-s’ivedh a

tot :sl of 83 units of i-ed cells, hepresenl i tug allout 11) ( 11i. of i ronu , She has (hevelllps’oh sI i glut

pignientation of the skin, but no alterations in glucose tns’tabolism or III 101’ s’videticc of

hemosiolerosis hi:ss been observed.

Summary: A 45 year old white housewife tws) veai�s ago devdlol)e(l s(’v(’r(’

anemia with associated decreased bone marrow erythropoiet u’ activity. Pleural

effusion appeared and a mediastinal tumor was (lemonstrate(l which on resection

proved to be a benign thymoma. Severe anemia persisted which did not respond

to administration of hematopoiet i(’ agents or s’ort-isone. Iransfusioui therapy

has been necessary to maintain the blood hemoglobin at livable levels. Skin

pigmentatiomi due to deposition of hemosideriui has appeared.




944 BENIGN ‘l’IIYM5IM.� \V1TII I1EFlh.-�(’TOlIY ANEM1.�

Fno. 11 -----1 list ologis’ scot i(I1u (If t unior fmoni c:tse nio. 2. i Ilust 1:11 li� p:llis:t(li tug of I lie spin-

olle sells IX 600).

FiG. 12.-- --1 list olslgic ss’s’t ion frotsi o’:tse 155). 2, i llust 1:11 i tig (Ills’ of I his’ liunsd’�’ous are:ss ilu

whiis:ht t he s1Ii nushli- I’s-I Is as’s’ :111:1 rigo’� I ti l’oset te-li ke f’orm:lI iOllS. Sc:l It d’l’ed lymllhiocvt d’s :tre

IIr0Ss-til I X S(X) 1

I )isci’ssiox

ihe l’liluid’al,�mtliologis’, ahidi hcnmtologic features (If our l)atiehits ate strikingly

similar. Ihe press’iis’e ot a severs’ anemia caused 1)0th pat ictits to seek medical

assistans’s’, and this anemia iii s-ash case was associated w’ith a marked decrease in

ervthropoiietis’ act ivitv in the marrow, w’his’h persisted in spite of all therapeutic




ROSS, FINCII, STREET, AXD STRIEDER 945

measures. There had been no exposure to toxic agents. Lymph node biopsies

were negative in both cases, and except for the mediastinal tumor there was no

evidence of other neoplastic disease. The acquired hemolytic anemia in case no. 1

appeared to be intercurrent and was completely relieved by splenectomy.

The tumor removed from each patient was a benign thymoma and the his-

tologic structure of the two tumors showed considerable similarity. No improve-

ment in the hematologic picture resulted from removal of the tumor, and both

patients have had to be given numerous transfusions to prevent the recurrence

of severe anemia. As a reflection of these transfusions, signs of transfusion

hemochromatosis have begun to appear.

The relationship between the benign thymoma and the etiology of the anemia

in our patients is of considerable interest. It is uncommon to find benign tumors

associated with anemia when iron deficiency and other specific anemias are

excluded. However, three instances of benign solitary tumor accompanied l)y

acquired hemolytic anemia have been recorded.24 Two of these were ovarian

dermoid cysts : splenectomy was w’ithout benefit, but following surgical removal

of the ovarian cysts there was prompt recovery from the anemia.3’ � Postoperative

death precluded the possibility of observing the effects of splenectomy and

resection of a dermoid cyst of the spletiic pedicle in the other case.2 The relation-

ship of the thymoma to the appearance of acquired hemolytic anemia in our

case no. 1 (patient L. L.) is not known, but the excellent response of the hemolytic

anemia to splenectomy is in sharp contrast to the results obtained in the other

cases of benign tumor associated w’ith acquired hemolytic anemia.3- � Our other

patient (E. T.) has at no time exhibited evidence of increased destruction of her

circulating erythrocytes.

The refractory anemias which occurred in our patients are unusual since the

only abnormalities consistently observed have been marked hypoplasia of the

bone marrow erythroid elements and associated anemia. Except for the transient

thrombocytopenia and leukopenia which developed iii patient L. L. during the

episode of acquired hemolytic anemia, the circulating leukocytes and platelets

have remained normal in number and morphologic characteristics and there has

been no evidence of extramedullary hematopoiesis. Possible “toxic depression”

of the marrow is believed to be excluded, since in neither patient was there a

history of exposure to any chemical substance known or suspected of being

toxic to the bone marrow. No deficiency of any hematopoietic factors has been

demonstrated in these patients, and no response to therapy with various

erythropoietic stimulants has been observed.

In a consideration of the relationship of these thymomas to the refractory

anemias, there are four possible considerations: (1) that they occurred simul-

taneously by chance alone, (2) that the thymomas caused the anemia, (3) that

the anemias caused the thymomas, or (4) that some etiologic factor was common

to both.

It is extremely difficult to predict. the statistical probability of chance oc-

currence of a benign thymoma and refractory anemia in the same individual.

However, it appears that the simultaneous chance occurrence of these two

entities would be extremely rare. In view of this it is of considerable interest- that,

in addition to the tw-o cases we have observed, there have been reported pre-




I)ate Sex Age Leukocytes Myasthe-and platelets nia gravis

1934 M 56 Decrease Yes

1935 M 20 Decrease No

1941 F 58 Normal No

1945 F 58 Normal No

Outcome

F

M

F

M

F

F

44 Normal

45 Normal

No

No

946 BENIGN TIIYMOM.-t W’ITII REFRA(’TORY ANEMIA

TAil LE 1 .- ‘I’h ynson�a 00(1 Refractory A nein ia-lie poi-ted Cases

Case Author

2

3

4

Opsahl

Hadojevic anidl Habit

Davidsohn

Huniphrevs aludl

Southw’orth

5* Wilutrolle 1946

6 Chalmers and Bo- 1953

heinier

7 Chalmers ansI Bo- � 1953

hseimer

S Chediak, Fuste, ahud 1953

Hosa!es -

U Hoss, Fillet), Street, 1953

:ttid St rieder

10 Ross, Finch. Street, 1953

llull St ris’ds’r

16 Decrease

45 Norma!

62 Norma!

47 Normal

Death

Death

Death

Thvnsoma resecteol

Anemia cured

Yes Deal ii

Yes Thvmotna resected

Anemia improved

No Thvnsoma ress’cted

Aliemia improved

No Thymoma rs’sectesi

Anemia cured!

Thvmoma resect cdl

Anemia unchanged

Thvmoma resecteol

Auuensia unchahugedl

* This 11:11 ient lund a hvperplastic I hynius, but no thynsonia.

viously or aFt’ known to us seven other instatices of a 1)enign tumor of the thymus

with associated refractory anemia (table 1). In 1934 Opsahl� reported a case of

thymic carciuioma amid aplastic anemia iii a 56 year old male w-ith myasthenia

gravis. ‘This patient had a severe paticytopema atid died following the gradual

development of agranulo(’ytosis. At autopsy a firm tumor ‘ ‘about the size of one’s

fist” ��‘as found in the upper anterior chest. There was no evidence of metastases

to bone marro�v or to other organs to account for the hematologic picture. On

sectioii the tumor consisted of fibrous bands interspersed with cellular areas and

areas of ne�’rosis. Scattered about through the tissue were l)ands of epithelial cells

arranged in palisades and resembling Hassel’s corpus(’les. Also present were many

irregular, polygonal ret icular eel ls w-ith oval, hyperchromat ic nuclei of uniform

size and with pale nu(’lei. Histologic description of the bone marrow prior to death

showed marked hypoplasia of erythroid and myeloid elements with absence of

megakaryocytes. At autopsy the marrow was yellow in color. The clinical course

and histologic description of the tumor suggests that it was a benign, rather than

a malignatit, thymoma. I)avidsohn,6 in 1941, reported a case of refractory anemia

in a 58 year old female in association with an upper mediastinal tumor. At

autopsy a firm, globular, encapsulated tumor w-ith a dark brown lobulated

sectioned surface enclosing smooth, homogenous, yellow nodes ��‘as found in

the upper anterior mediastinum. Microscopically the tumor ��‘as composed of a

network of polygonal and spindle-shaped cells enclosing groups of large cells

with vesicular nuclei and fat-rich cytoplasm. Rudimentary Hassel’s corpuscles

were seen and the ��‘hole picture was compatible with a lymphoepithelioma of

the thymus. The marrow showed a definite decrease in red cell precursors along

w’ith normal myeloid and megakaryocytic elements. Humphreys and South-

worth7 have reported the occurrence of a refractory anemia in a 58 year old

female associated w’ith a benign epithelial tumor of the anterior mediastinum.

The bone marrow showed only mild hypoplasia of the erythroid elements.




ROSS, FIN(’iI, STREET, AND STR1EDER 947

Following surgical resection of this tumor the hematologic picture ��‘as restored

rapidly to normal. The tumor appeared to be of thymic origin and consisted of

degenerated Hassel’s corpuscles, spindle-shaped cells, aiid lymphocyte like (ells.

At autopsy one year later no evidence of any tumor ��‘as found. Radojevic and

Hahn5 reported the occurrence of a benign thymic tumor and pancytopenia in a

20 year old male. At autopsy a cystic fibrous tumor of the thymus gland and

extreme hypoplasia of the bone marrow was found. Prior to death x-ray therapy

was administered to the tumor and it svas thought that the cellular elements of

the tumor had beets destroyed.

Chalmers and Boheimert have observed a 48 year old male with myasthenia

gravis who suddenly developed a profound anemia without evidence of hemor-

rhage or hemolytic disease. His red cells were normocyti(’ and normochromic and

his white cell count was normal both in its total and differential values.

Heti(’ulocytes were absent on numerous studies. Bone marrow- biopsy showed

absence of all recognizable red cell precursors, although leukocytic aiid

megakaryocytic elements were normal. The anemia failed to respond to “all

available hematinics including ACTH” atid the patient. had to 1)e treated �vith

transfusions. Repeated x-rays of the chest did not reveal a thymoma, but “he-

cause of the know-n connectioti of thymoma amid myasthenia gravis as well as the

rare reported cases of anemia in association with a similar tumor,” operation

%vas performed and revealed a large thymoma w’hich invaded the mediast.inal

pleura locally but showed no other signs of malignancy. Removal of the tumor

was followed by a return to normal of the red cell precursors of the bone marrow

and in five days the first reticulocytes appeared in the peripheral blood, and

in a short time rose to 20 per cent. In less than three weeks they dropped to nil

again, and the bone marrow regressed to the erythroid aplasia which existed

before operation. Subsequently the patient’s spleen enlarged and his myasthenia

which had improved with operation was also relapsing. Splenectomy was later

performed and this ��‘as combined with large doses of ACTH. Favorable re-

sponse of bone marrow and peripheral blood again oc(’urred which lasted for

three weeks. Relapse again occurred and a further course of ACTH w-as given.

On the sixth day of ACTH treatment reticulocytes appeared and the marrow

showed numerous erythrohlasts. He has now been followed for one year without

evidence of relapse of anemia or myasthenia gravis.

Chalmers and Boheimer9 have observed a second patient with this syndrome

and have kindly agreed to allow us to (‘ite it here. This patient, a female aged

62 years, had a severe anemia refractory to “all usual therapeutic measures,” but

when given ACTH remained well for six months in contrast to the period before

ACTH therapy when she required transfusion every three weeks. At the end of

the six month period she again relapsed, and the second course of ACTH was

without benefit. A large mediastinal tumor was demonstrated by x-ray and the

tumor, a thymoma was removed. Slight transient hematologic improvement

followed the operation l)ut she again relapsed. After 100 mg. of ACTH a day for

ten days reticulocytes appeared and numerous erythroblasts w’ere present in the

marrow which previously had shown no erythroblastic elements. It appeared

that this remission w’ould also be transient.

Chediak, Fuste, and Rosales’#{176} report the case of a 47 year old white male




948 BENIGN TIIYMOMA WITH REFRA(’TORY ANEMIA

with profound normocyti( anemia and complete aplasia of the erythropoietic

elements of the bone marrow- . The leukocytes and platelets of the blood and

granulopoietic and megakaryocytic elements of the marrow were normal.

Multiple hematinic agents �vere ineffective in relieving the anemia, amid tratis-

fusions were necessary. All anterior superior mediast-inal tumor was demon-

strated radiographically, and this was removed surgically and proved to he a

thymoma. Reticulocytes appeared in the blood twenty-four hours after operation

and increased to 18 per cent on the sixth day. Red sell elements appeared in the

marrow and the peripheral blood returned to normal and remained so.

Wintrobe mentions in his textbook,” and has provided us with additional

information oti,1� a 16 year old girl with myasthenia gravis of fourteen months

duration ��-ho developed purpura and pancytopenia of undetermined origin

after having heeii treated w’ith guanidine and prostigmine for five months. The

hematocrit ��‘as 22 pet’ cent, platelets 30,000, and leukocytes 1700 to 3600, with

60 per (‘chit lymphocytes. Guanidine was stopped and she was treated with

transfusions but died seven months later of ruptured corpus hemorrhagicum

and hemoperitoneum. lie bone marrow was hypoplastic with complete absence

of megakaryocytes. The thymus gland, w’hich ��‘as at the upper limits of normal

for this age,’3 weighed 38 Cm. ; its color, consisten(’y, and lobulation ��‘ere normal.

The mi(’roscopic structure ��‘as not remarkable except for an increase in lympho-

cytic elements. This case is dissimilar to the others reported here, and it is not

clear �vhether or not the hypoplasia of the marrow’ ��-a.s a result of the medication

the patient had beeti given, or was idiopathic, or was in some way related to the

presence of the enlarged thymus gland.

All seven of these patients had “benign” tumors of thymic origin which appear

to be similar (although perhaps not identical) with those of our patients. They

all had decreased erythropoietic activity ill the bone marrow, and anemia

refractory to all therapeutic measures except transfusion. In four cases, as well

as in our own two patients, leukocytes and platelets of the blood and granulo-

poietic and megakaryocytic elements of the marrow were normal even though

there was almost complete absence of erythropoiesis. In tw’o patients there was a

decrease in leukocytes and platelets in the blood, and a marked reduction in

granulopoietic and megakaryocytic elements in the marrow. Both these patients

died, whereas only one of those with normal leukocytes amid platelets succumbed.

It is possible that the presence of these thymomas was responsible for the

appearance of the refractory amiemias. In most endocrine glands (i.e. thyroid,

hypophysis, adrenal, parathyroid, amid islets of Langerhans), hyperplasia or

neoplastic change induces metahohc disturbances which usually represent some

alteration of their normal function. However, the normal function of the adult

thymus gland remains shrouded in mystery in spite of well over 2000 publications

on this subject during the past forty years. Many clinical amid experimental

observations have related thymi(’ function to disturbances of almost every

system of the body, hut tione of these reports- have been confirmed. On the other

hand, there is some evidence that the atrophic appearing thymus of the adult

may be physiologically active. While much fatty and fibrous replacement of the

involuted gland occurs, many foci of thymic and syncytial cells remain.ti The

l)est chni(’al evidence for a systemic effect of the hyperplastic thymus gland is in




ROSS, FINCH, STREET, AND STRIEDER 949

myasthenia gravis where thymectomy may be palliative.’5 Mamsy investigators

over a period of years have attempted to ascribe various hematopoiet-ic effects in

amsimals and human subjects to either the administratioms of thymic extracts or

resection of the thymus gland. These observations have consisted of changes its

the msumber of circulating leukocytesm622 and erythrocytes,’#{176}- 20, 23, 24 but the

results obtained in most of these studies are subject to cotisiderable criticism.

It w’ould have heels of considerable imsterest had extracts of our patiemits’ tumors

been prepared amid the effect of such extracts on the hematopoietic svstem

evaluated by in vivo experiments. Unfortumsately, rio extracts were prepared.

The best experimemstal evidemice for a thymic influetice omi hematopoiesis is

provided by the studies of Furth, et al.25’ 26 These investigators ��‘ere able to

reduce the incidemice of leukemia in a high leukemic stock of mice from 80.8

per cent to 9.9 per cemit by thymectomy.

Other experiments by T.ptoti and Furth27 itidicated that although inhibit-ion

of spontaneous leukemia in mice was obtaimsed by producitig lymphoid and

thymie atrophy with cortisomse, more effective imshibitioms s�’as obtaitsed by com-

plete surgical removal of the thymus. This suggests that the reticular matrix

of the gland (which is not sigisificamstly altered by cortisone) may retaits its

capacity to allow or to promote leukemia development.

Kirschbaum amsd Falls28 report that thymectomy also was effective its re-

ducing the incidence of carcinogen-imiduced leukemia iii mice. These studies

suggest that some relatioms does exist betweems the thymus amsd the hematopoietic

system, although the exact isature of this relatiomsship is obscure.

Climiical evidence supporting a possible causative relatiomsship betw-eemi the

thymic tumor and erythropoiesis is provided by our case no. I , in which the

tumor was known to exist for three years before the developmemst of anemia,

amid by the fact that removal of the t-hymic tumors of the cases of Humphreys,7

Chalmers and Boheimer,#{176} amid Chediak’#{176} resulted in improvemeist or in cure

of the anemia. In comstrast our patient-s were not relieved by resection of the

thymoma. It must be coticluded that the evidence supporting etiologic relatiomi-

ship of the thymoma to the anemia is suggestive, but Isot defimmite. In our two

patiemsts the thymus glatid was isot removed at the time the tumor was resected,

and the possibility must he comssidered that persistemice of thymic tissue may

have a continuing adverse itifluemsce on erythropoiesis. It is interesting to speculate

as to the possible beneficial effect that removal of the thymus glatid itself might.

exert on our patietsts atsd On certain other cases of refractory anemia.

The third possibility is that the refractory anemias may have produced the

thymomas. Although chronic tissue alsoxia may produce tissue destruction and

fibrosis (e.g. myocardium), it is not recogtsized as inducing neoplastic parenchymal

change. It is quite improbable that the botse marrow is capable of elaborating

any substances which might be responsible for the development of the tumors.

Furthermore, the presetice of the tumor is known to antedate the developmemst

of the anemia in at least one case.

A possible explanations for the simultaneous occurrence of these disorders

is that they both have 1)een produced by a commomi etiologic factor. The adult

atrophic thymus glamsd may rapidly assume its maximal prepuheral size its

response to adremsalectomy, castratioms, hypophysectomy, partial thyroidect-omy,




950 tiENIGN TIIYMOMA \VITtI ISEF1SACTOSSY ANEMIA

hypert-hyroidism, Addisoms’s disease, dietary changes, drugs, inactivity, allergy,

and imsfectioms.29’ �#{176} Rapid atrophy may o(’cur under the iisfluence of steroid

hormomses, stress, dietary chaisge, and certain drugs.29’ 31 The principal agemits

w’hich have beets iti(’rimiiiated as a cause of refractory atsemia have been the

derivatives of henzol, atid it is interesting that methyl cholamithretse has beets

showts to produce thymic hyperplasia.32 More receistly vari()us hormones, amid!

particularly the steroi(ls have beets showts to he important hematopoietic

regulators. The polycythemia of Cushiisg’s disease and the atiemias of hypo-

pituitarism, Addisoti’s disease, amid hypothyroidism are all strikimsg clitsical

examples of this hormone iisfiuemice. The I 1-17 oxysteroids appear to have a

profoumid effect ots the msuml)er of circulating gratiulocytes, lymphocytes,

eositsophils, amid reticulocytes. The apparemit effect of these steroids oti both

the thymus atid l)one marrosv may be sigtsificatst, especially sitmee it has heetm

clearly sho�vn that estrogemis are capable of ims(lu(’imsg prea(letlomatous thymis

(‘hatsge.3’ However, neither of our patients atsd noise of those reported its the

literat ure has demomist rated any recogmuzable endocrimsopat hy. The presence of

myasthenia gravis in two patietsts is worthy of msote, hut its relationship to the

thymoma amid the amsemia is utsktsowms.

Irrespective of the etiology of this utiusual combitiatioti of disorders, there is

good evidemice that it is not a (‘hamsce occurretsce amid that they are etiologically

related. Therefore it is justifiable to recommend careful study of the thymus amsd

of the bomse marrow whemsever either thymoma or refractory anemia is observed.

Eveis if the thymus is not overtly enlarged its cases of refractory anemia it is

possible that there may he siglsificamst deviatioms from the msormal histologic

pattern, or as in Boheimer’s case, actual thymoma may 1)e present which catimsot

l)e visualized by radiologic study. In view of the marked clitiical improvement

which followed resection of the thymoma iti three cases the advisability of

surgical exploration and possibly of resectioms of the thymus should be comisidered

imi patiemits wit-h refractory anemia, particularly those with hypoplasia or aplasia

of erythropoietic elemetsts of the boise marrow.

SUMMARY

1. The simultamseous occurretice of a betsigis t-hymoma amid a severe anemia

which failed to respomsd to therapy with recognized hematopoietic agetits has

beets observed its two adult female patiemsts.

2. Reports of seven other patients with a similar associatioms of thymoma

amid refractory anemia have beets foumsd atsd the ,saliemst features of these oases

are summarized.

3. Possible explatsations of the simultamseous occurrence of these two ummusual

conditions are discussed.

4. It is suggested that the thymus glaisd or tumors of the thymus may he

etiologically responsible for certaits cases of refractory atsemia.

SUMMARIO IN INTERLINGUA

I. Ha essite observate in duo adulte patientes feminin le occurrentia simultanee

de tin thymoma benigne e un sever anemia que non respondeva a! therapia con

le agentes hematopoietic normalmente empleate.




ROSS, FINCH, STREET, AND 5TRIEDER 951

2. On ha trovate reportos de septe altere patientes in qui thymoma e anemia

refractori esseva similemente associate. Le tractos saliente de iste casos es

summarisate

3. Possibile explicationes del occurrentia simultanee de iste duo conditiones

inusual es discutite.

4. Es considerate le possibilitate que le thymo o tumores del thymo es etio-

logicamente responsahile pro certe casos de anemia refractori.

REFERENCES

t POPE, R. H. AND OsGool, R. : Reticular perithelionia of the thymus. Am. J. Path. 29:

85-103, 1953.

2 SUAREZ, C. V. AND ETCHVERRY, M. A. : Quiste dernsoides del hilio esplenuico, esplenonie-

galia, icterico hemolitica y niamia grave. Anionsahias lobula del spiegel. Lobula ab-

berante hepatico. Arch. argent. de enferns. d. ap. digest. y ole In nutrici#{243}ni. 12: 168-185,

1936-37.3 WATSON, W. N. W. AND YOUNG, C. J. : Failed splenectomy in acholuric jaundice, andl thue

relation of toxaemia to the haemolytic crises. Brit. M. J. 1: 1305-1309, 1938.

4 SINGER, K. AND DAMESHEK, W. : Symptomatic hensolytic anemia. Ann. Int. Med. 15:

544-563, 1941.

‘ OPSAHL, R. : Thymus-karcinom og aplastisk anemi. Nord. med. 2: 1835-1836, 1939.6 DAVIDSOHN, I.: Hemochromatosis, thymonsa, severe anemia anid endocarditis in a womanu.

Illinois M. J. 80: 427-432, 1941.

HUMPHREYS, G. H., II AND SOUTHWORTH, H.: Aplastic ahiemia terminate(l l)y rensoval of

mediastina! tumor. Am. J. M. Sc. 210: 501-510, 1945.

8 RADOJEVIC, S. UND HAHN, A.: Berinflusst der Thymus die Zahl der Granulozyten? Str:slu-lentherapie 53: 90-101, 1935.

#{176}CHALMERS, J. N. M. AND BOHEIMER, K.: Personal consmunication.10 CHEDIAK, A. B., FUSTE, R., AND ROSALES, G. V.: Timoma y anemia aplastica. Archi. del

Hosp. Univ. 5: 27-39, 1953.

hi WINTROBE, M. M.: Clinical Hematology, Ed. 3, Philadelphia. Lea & Febiger, 195!, I�P#{149}

533.12 WINTROBE, M. M.: Personal communication.13 BOYD, E.: The weight of the thymus gland in health and disease. Am. J. Dis. Child. 43:

1162-1214, 1932.14 HAMMAR, J.: Ueber Gervicht, Involution und Persistenz der Thynsus im Post fotallenuben

des Menschen. Arch. f. Anal. u phys. Anal. Abtlg. Suppl. 92: 91-182, 1906.

16 SCHWAB, R. S. AND LELAND, C. C.: Sex amid age in myasthenia gravis as critical factors

in incidence and remission. J. A. M. A. 153: 1270-1273, 1953.

16 PATON, D. H. AND GOODALL, A.: Contribution to the physiology of the thymus. J. Phys-

iol. 31: 51-64, 1904.t7 PIGHINI, G.: Studi sul timo, IV. Sugli effeti della tinsectomia. Rev. sper. di frenuiat.

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1954 9: 935-952

JOSEPH F. ROSS, STUART C. FINCH, RUSSELL B. STREET, JR. and JOHN W. STRIEDER The Simultaneous Occurrence of Benign Thymoma and Refractory Anemia

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