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pasien tumor mediastinum s.thymoma dengan anemia yg berulang
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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
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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).
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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.
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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
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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
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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
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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
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.� ‘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.
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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
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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-
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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.
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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
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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
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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,
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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.
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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.
Reggio-Emilia 46: 1-86, 1922.‘� B�mo, G.: Ii timo studiato neghi effetti complessive della stimizzazione sperinsentale.
Policlinico (sez. chir.) 24: 197-219, 1922.1� ZONDEK, H. AND KOEHLER, G.: Blutbild und innere Sekretion (Polycythutmie, Anuamie,
Leukhmie) Klin. Wchnschr. 5: 876-881, 1926.20 DE CANDIA, S. AND FLORLANI, F.: Azione del timo sull’ empoiesi e sulla nsilza. Pohiclinuico
(sez. prat.) 45: 1553-1556, 1938.21 REHN, E.: Die Hyperfunktion des Thymus als Kranikheit. Deutsche med. Wchnschr.
66: 594-597, 1940.22 BROMSKOV, C. AND KRAFT, K. H.: Die thymogene lymphocytose. Pflugers Arch. ges.
Physiol. 243: 623-633, 1940.23 DE CANDIA, S. AND PELOSIO, C.: Arizone del limo nell’ avitaminosi e sperimenutale. Nata
111-Studio isotologio del medallo osseo, della milza, del fegato e del surrenii. ()rmoni
5: 373-383, 1940.
For personal use only.on September 3, 2015. by guest www.bloodjournal.orgFrom
952 BENIGN THYMOMA WITh REFRACTORY ANEMIA
24 -: Thymus und Blutbildunug. KIm. Wchnischr. 21: 648-650, 1942.�#{176}MCENDY, D. P., BooN, M. C., AND FURTH, J.: On the role of the thymus, spleen and
gonads in the development of leukemia mu a high leukemic stock of mice. Cancer Re-
search 4: 377-383, 1944.26 FURTH, J.: Prolongationi of life with prevention of leukemia by thynsectomy in mice.
J. Gerontol. 1: 46-52, 1946.27 UPTON, A. C. AND FURTH, J.: Inuhibitionu by cortisone of the olevelopment of spontaneous
leukemia and its inductions by rasliat ion. Proc. Am. A. for Cancer Research 1: 57, 1953.
28 KIRSCHBAUM, A. AND FALLS, N. G.: Inuflueruce of androgenic hormone on the carcinogenic
inductiomu of leukemia. Proc. Am. A. for Canucer Research 1: 30, 1953.
2� SELYE, H.: Textbook of Endocrinology, Monut real. Ada Endocritsologica, 1949.
30 WILLIAMS, H.: Textbook of Endocrinology, Philadelphia, Saunders, 1950.
31 Ross, M. A. AND KORENCHEVSKY, V.: The tluymus of the rat and sex hormones. J. Path.& Bad. 52: 349-360, 1941.
32 STEtNER, P. E.: Epithelial hiyperplasia of Hassel’s bodies of thymus gland induced by
methylcholansthrene. Proc. Soc. Exper. Biol. & Med. 4.9: 62-67, 1942.
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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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