From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

B L Q Q ID
OCTOBER,

The

Journal

1954

The

VOL.

Simultaneous

Occurrence

of

Refractory
By

F.

JosEPh

Ross,

C. Fixcit,

STrAJLT

HE

PRESENCE

failed

W.

our

clinic

states

of a benign

to respond

to all

in

between

probability

the

which

This

eases.

is

one

evidence

connecting

herewith

the

summary

link

to

the

thymus

clinical,

of the

No.

gland

reported

have

an

year

anemic
hospitalized

The

followig

at

normal

nucleated

cells
she

recurred,
that

time

From
arid

and

of our

the

Surgery,

to
or

blood

chain
of
We report

patients

to
to

Robert

icterus.
in

with

diameter;
Evans

This

was

University
18,

supported

One

Memorial

to

any

hematopoietic

cells

in the

later

years

later
to he

were

freely

Memorial,

moval)le

the
and
of

Medicine,

for

publication

a contract

Hospitals.
935

and

Departments
the

lymph

between

of
or

again

other
and

well

were

of Pathology

and

of Medicine,

node

inquiry

to

history

pale,

multi-

alleflhia

There

sub-

family

nourished
palpable,
was
Thoracic
Pathology

Mass.
8, 1954.
Atomic

Energy

for

it was

Careful

nontender.

February
the

marrow

nodes

Departments
Boston,

and

large,
lymph

in

hone

Past

axillary

mark-

erythropoietic

axillary

derivatives

revealed

and

(194$)

anemia
of

Hospitals.

benzol

examination

her

symptoms

function.

supraclavicular

by

An

com)letely

found

increase

cells,

found

was

was

appeared,
and she
of whole
blood.

of

Memorial

of exposure

accepted

in part

month

Massachusetts

School

1954;

sts

number

a generalized

and

disease.

Hospitals

she

investigation
a decreased

multinucleated

they

( 1945)

51w
Three

afl(i

Heed-Sternberg

Physical

Memorial

Boston

for
showed

of the

impair

The

Dawson

January

the

a history
negative

visible
2 cm.

basis

ago

1)all)itation,
and (l\-spneoL
received
several
transfusions

biopsy

Hodgkins

elicit

essentially

Massachusetts

the

on

exploration

hospitalized

of

years

examination

appeTtre(l,

elements,

suspected

Submitted
work

again

eight

surgical

\Veolkness,
where
she

admitted

Massachusetts

the

the

system.

details

x-ray

headaches

suggestive

had

was

failed

1 to

Surgery,

hut

she

without

averaging

as

were

prol)al)ly

were

female

refused

frontal

granulocytopoietic

known

history

and

nebulous)

hematopoietic

housekeeper,

by survey

aspiration

which

and

onid

marrow

negative,

was

tinw,

she

month

elements,

stances

thymus

a
similar

seven

REPORTS

fenntle

maSS

local
physician
a local
hospital

her

Bone

that

in

pathologic
a probable

of

frequently

morphologic

which

observed

abnormality,

reports

in the

the

been

erythropoietic
of

(and

anemia

recently

cases.

white

internittent

by

transfusions.

at

that

severe,

edly
was

single,

mediastinal

at

numerous,

felt

01(1,

anterior

asymptematic

biopsy

AND

of two unusual
of time suggests

finding

with

and

.Jn.

12. IL. , a 44
to

has

of abnormalities

hematologic

10

and

STREET,

of a refractory

the

the

legendary

CASE

Case

and

by

the

previously

and

occurrence
brief period

tumor

coincidence

more

B.

measures

strengthened

unusual

provides

Thymotna

RUSSELL

thymoma

therapeutic

thymic

NO.

STRIEDER

in two patients.
rfhe
simultaneous
two patients
within
a relatively

relationship

Benign

IX,

Anemia

Joux

of Hematology

Commission

an

From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

936

1)IXIEN

lu;.

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that

coupled

use

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oil

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red

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rate

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physical

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read

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fragility

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ruct

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anemia

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findings

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tell

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to

oms

test

apparent
ion

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5.02

not

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survival

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1948

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From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

115)55,

was

December

performed!

(ongestive

changes

this

big

the

struction
on

Coombs
15,

1949.

following

She

2-llist

Fio.

(X
sence

elements

850).
FIG.
3,-Stained
of

became

The

ervthroid

to

show

ologic

the

and

and

sect

and

of

ion

hone

marrow
IX

cell

red

bone

cell

marrow
(S

aspi

SO

rat

are
ion

smear

no

450

other

1949);

the

by

Ashbv

I lie

which

rate

and

showed
Follow-

of erythrocyte
te(hini(,

been

had

Gm.

abnormality,

low

denormal

was

ret urne(1

to

nor-

sihlc(.

ion

forniat

:111(1

(as(

from

l)resent

weighed

hut
13,

937

EDEE

spleeti

counts

remained
of

972).

The

survival,

leukocyte

evislence

STill

anemia,
(January

red

have

megakarvocvt

elements

ill effect.

negative
and

platelet
an

.\ND

of hemolvtic

normal;

splenectomy

failed

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test
to

STREET,

I,

without

1948

characteristic

returned

March

mal

15,

FIN(l

but
from

no.

one

1.

ervt

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case

115).

months

The

later

marrow

is

e Precursors
1 , demonsi

sas

are
rat

big

again

cellular;
absent

t he

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From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

938

l1l-NI(iN

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From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

11US$,

FIl.

cells

5.-Histologic
tetuding
to

FIG
cells

st rable
(lid

The
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see t i on

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seriters

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surgical

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chloride

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liver

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year

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ensuing

STREET,

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6.-Histologic

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1101

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Ii

B12

From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

940

BENIGN

by

injection-all

without

administered
mg.
cyte
deep

for

and
to

binding

cast,

protein

glucose

effect.

days,

and

Neither

of

these

and

her

at

many

transfusions,

is com)letely

the

beneficial
days.

especially

its

over

In

1950,

80 tng.
1951

substances

Polyuria,
diabetic,

the

was

gradually

and

face.

was

given

100

erythro-

past

has

three

years

developed
The

nocturia

and

insulin

therapy

and

of ACTH

she
stimulated

During

skin

forearms,

iron.

is typically

July

December
rate.

hand,

with

test

ANEMIA

in

customary

the

saturated

tolerance

REFRACTORY

six

recurred

receive

grayish-brown

for

fifty-two

anemia

continued

appeared,

daily

daily

production
has

WITH

demonstrable

intramuscularly

of cortisone

she

TI! YMOMA

plasma

iron

glucosuria

have

is now

neces-

5T1 ry.

This
has

patient

received

additiotial

now

has

a total

of

I)one

gressive

marrow

increase

in

months

ago

Eight

indicated

Fe59

1 per

cent

after

the

tumor

was

anemia

developed

poietic

elements.

lieved

by

and

which
of

of transfusion

five

Gm.

of

years

and

iron.

Three

except

for

pro-

time

study

studies

disappearance

time

circulating

was

repeated

employing

the

of Fe59

red

blood

with

cells

and
radio-

less

than

three

weeks

which

marrow
type

and

in

any

relief

as well
been

only

with

given

to

of the

anemia.

ACTH

and

As

have

to

be

Treatment
cortisone

of

and

and

a half

a thymoma,

all

not

benefit

known

and

the

severe

reThe

hundred

a consequence

was

change.

with
did

one

appeared

in erythro-

Four

proved

transfusions,

date.

hemochromatosis

persisted.

and

a severe

and

congestive

anemia

sub-

ago

appeared

only

severe

blood

years

decrease

anemia

removed

as with

asymptomatic

Five

a marked

revealed

was

an

ago.

showed

which

tumor

whom

in

years

of hemolytic

marrow

result

have

woman

the

seventy

transfusions,

diabetes

mellitus

developed.

Case

No.

E.

T.,

pitals

a 45 year

two

left
ness,

and

was

old,

years

ago

Two

months

slight

fever.

chest.

and

she

transferred

tory

of exposure

marrow.

nodes

1 and

seventh
below

rib
the

3 cm.

in

other

agents

review,

and

The

costal
findings:

the

heart
in the

was

negative.

per

cent,

left
left

was

margin
Urinalysis
31.0

the

in
over

not

negative,

two

The

The
line.

Hinton
10.8

The

per

Gm.

per

liver
spleen
red

was
blood

MCV

was

of a well
she

was

There

was

no

his-

to

the

bone

Physical

distress.

The

movable
to

below

the

was

percussion
level

palpable

cu.

3.55
,

skin
lymph
of the

palpable

count
87.2

ad-

and

toxic

not

cent,

and

dullness
edge

the

before

presence

iso acute

and

cent,

weak-

heart,

nontender,

negative,
Gm.

the
of the

showed

remarkable.

cough,

anemia

of being
in

chest

iii

noncontributory.

firm,

anteriorly

her

Hos-

a mass

weeks

surgery.

were

thorax

midclavicular

hemoglobin

for

female

were

axilla.
lower

side

or suspected
pale

There

of

revealed

left

history

intelligent,
pallor.

time

Hospitals

family

of 3.6
Two

recurrence

of the

known

nonproductive

therapy.

at that

aspect

and

a hemoglobin

and

Memorial

for

diameter

sounds

posteriorly.

hematocrit

to

pain

x-ray

anterior

a cooperative,

examination

Laboratory

or
system

except

breath
right

neurologic
ml.,

benzol

remarkable

absent

the

with

Memorial

weakness,

transfusion

chest

Chest
on

Massachusetts

a dry,

anemic
for

the

cough,

developed

be

left

Massachusetts

revealed

not

to

aching

to

of a dry

hospital

transfused,

history,

admitted

she

found

local

situated!

to

Past

was
her

the

was

complaining
admission

dull,

to

examinatioti

with

She

and
mass

then

was

before

developed

tumor

housewife,
1951)

at

hospitalized

again

defined

white
(May

hospitalized

mission

cu.

past

40
change

survival

in the

eight

spleen

is controlled

four

essential

same

plasma

white

bone

the

agents

signs

has

of

not

hematopoietic
anemia

cent

that

appearing

acquired

mediastinal

did

no

transfusions
At

single

the

An

the

this

Ashbv

demonstrated

erythropoietic

ago

but

50 pe

old

first

removal

hypoplastic
years

revealed

the

about

administrations.

A 44 year

Summary:
sternal

the

radioiron

during

represents

hemosiderin.

survival.

hour

This

have

1952)

a 9.9

admissions

cells.

of marrow

injected
of

red

examinations
(April

showed

hospital

of

ervthrocvte

of the
time

thirty-nine
units

amounts

a normal

isotope

had
174

4 cm.
and!

the

million/
MCH

30.8

From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

ROSS,

FliT.

7.-Posteloariteliot

atuteriol-

X-1a\

nioved,

t here

is

34.9

ps

NICHC
and

cytes,

white
cent

ervthrocyte

test

was

a tionprotein

alhunsits

of 3.58

the

presence

left

lower

the

i)ar:ttracheal

left

chest

nal

marrow

mature

ant

greatly

lat eral

:111(1

gross

X 6.5

scribed

in

dense

previous
*

s-ompletion
22,

base

adverse

the

previous

tumor

but

meti
Gm.*

has

This

scat

previously

of

P05I

of

iohu

nig.

flui

(rI)-

I te

edit

few

:1

normal.

it was

was

felt

A spherical,

Ilr(serit
ilicreas5

luolle

probably

ietit

t hsora-

exlllotat

sry

tumlIl

masS,

I his- lIft

froni

ill

Is-s-I ule,

all-ho

this- pat
atu

removeol

was

um,

81cr-hiefly

wIle

tuohul)es!unculatell,

llli

cells.
S(riss.

slight

t hat

hlronchioscopy

of
t lie

S :511(1 #{182}H.
1tt hiroill

lynsphi

Isormal

stushies

a negative

ic

Ilrsstlrsl)ls

Thud-Id

ion
ftom

tumot

for

g1aluulosyt

cell

7 ) , The

I fig.

lemovssl

(figs.

red

s(-rum

leveale(l

(alsifis-at

fluid

hoI)e

utuits.

-etit

X-laV

oxlellsive

lit

( )t Iis-t St ulli(-s

1151

(huest

negative

glanulo-

\Vi

7.5

nsesliastiluuni

t lie

(If

ls

ilidex

Gtn.
.

tue

lllll)Iui

1501155:11

6.48

coloted

was

eo5i

was

25$,()tX)s-tu.

lila)

is-Islic

of

st raw

ievealesl

I)erica

thse

((lull)

(elit

selut

nsetamyelocytes

hut

sohusist

NI of a

ihuterlacing,

surface
fitie,

:1

t umot

masses

(If

cells

uhuifornily

amid

heels

described

gra-whuite

were

cells

tered

was

composesl

This spilsdle

by

I urisslt

sensiencapsulatell

Thus exterisal

with
revealesl
h)ahsds,

were

the

IT. Thus-

lying

:ttit

srislr

sequelae,

270

case.

fibrocollagenous

of

4 I)(h

p1s)teils

hut
and

1951.

speci

lobules

total

Isyperplasia

of these

otu May

examihiatioli

case,

This

ansI

cc.

biopsy

, II1II5l(t

itu the aiutei-ior

, amid there
:ts

wet-c

Followihug

t he

niass

huumhel,

node

1 1)01) cc

of 73 I)(t

, alud

of 0,3

present

markss!
ihi

a tish

((lit

excret
,

bilirubits

I union.

weighing

of whorls

histologic
by

and

csnt

of lymphocytes,

lymph

to) t lie
i Oh

inspect

cm.

(corrected)

megakaryocytes

the

wit hout

:115(1

leukoeyles

and

Upon

nss)huosytes

t housarud

numbers

I)5I

dliffenehstial

per

WaS

(hue

0.3
:t

tunsot

flubh

slecreasesl

performed

num

posed

defines!

11:11 is-lit

on

IIelfottiselh

urobilihsogelu

, ahssi total

tis)(les.

chest

was

On

9.5

fecal
24 (.Ini.

demonstrated

course:

medliasti

inni./hir.

polymorphonuclear

a malignant
elior

34

well

cells.
Left
axillarv
evidence
of tumor.

cotomy

rate

cent

elenseruts

ItO

remit

alud

large

were

Clinical

6 per

of

aspiration

with

es,

atelectatic,

contained

count

inns.

shiest

Ileelu

lobe.

letisulocyte

nitrogen

lyniph

Granulocytic

had

was

lowel

left

9-11

ST1IIEDER

d)f

hu:sd

t lie

10,450/cu.

per

AND

x-ta\s
esis

negative

of a large,
lobe

elenieusts

plasma
and

Gm.

lateral

hiotasetut

Tue

sedimentation

Coombs

of the

cent

lynsphost

revealed

of

count

STREET,

left

aftel

collapse

blood

17 l)s

The

alill

niade

\VTIS

ahisi

miss.

FINCh,

slid

fihlous
t lie

(If

divided
tuot

satiie
into)

folm

laIge

ilicoluspicuous!v
Pope

and

tiueastu

pinkishu-gta.

s) 1:111115

t \VO

large,
solid
amotig

(isgood1

atsd

ii

firm,

1 fig.

I YI

(If

ilrl-gulal

is their

COhU-

10).
cell
sIclslhlules

massss
I hue

10 X

rig

:11111

IS ill

this

lvtusphiocytic
case

no.

7.

From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

942

BENIGN

Fi s;. S. -Histologic
megakaryocyl
(X

--SI

are

dIri

of

IIEFRA(TORY

tuarrow

Ilut

marrow

hotie

WITh

hone

nuunserous,

ai tied

elyt

smear

from

(-ass

hurs)I)oietic
from

ANEMIA

rio.

2. Grariulocytopoissis

activity

-ase

no,

is

gt-sat

2. No) ervt

Ii

ron

lv

is active,

rsdusssI

d slemstu

Is

(X

600).

rs

sSsll

:t

972).

sells.

in

soms

sallell

or

wholhssl

were

riolt

demolist

ret iculuni
groups

sect

es

Fl s;. U

TI IYMOMA

libels
(If

sPlhs

:(leas,

11);

rable
were
01

thuss tehlded

however,

(fig,

ill

in
scat

itsslivishuah

(It her

t lie
tored

ioset

:sreas

Ic-like

I hsroughout
sells.

Hassel

to group

togethel

t hss formedl
areas.
and

us small

rosette-like
Collagen

nests,

st ruct

ures

olepositis)n

only

occasionally

s corpuscles

\\sls

was
slid

hot

t hey

aIlI):irent

sometimes
(fig.

12)

pali,

Fibrils

inconspicuous,
sul-rounud

small

From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

BOsS,

FIXCII,

STREET,

AND

943

STII1EDER

Fm.

Following

t o 42 pcI

One

nsonth

weakness,

oonsisted

Physical

finohings

red

blood

l)C cent
tiornial
were

Platelets
differential
.

t o 45 er
transfused

erit

from

19.5

to

anemia

ities

of
:sl of

past

and

of
of

hemosiolerosis

hi:ss

with

effusion

to

be

been

22,
ial

lI:IyS

olurat

Laborat

fIlbns

left

or

The

ansI

:tggluti

Novsniber

nat

iotu

iii

15,

st udy

I ralusfused
100

nig.

aoselerat

skin,

continues!

any

bsen

hepresenl
but

of

11i.

glucose

i ronu

of

p110
-

She

she
has

tnstabolism

or

luct

:11111

i s)tu.
folio

She
:11-ill,

for

No

ahbluornial-

hi:ts

rso-sivedh

(hevelllpsoh
III

o-

period

hisrapv

ion.

psrio)(!
,

hemat

for

iotu

prooluct

tluis
of

1 survival

iou

I ralisfusil)11

regular

hiros-vte

I)uring
11) (

in

re

ervt

obssrveol.
tug allout

alterations

no

to) r(slui

evidence

(tuu.

hue huematoo-rit
tustzsia

slaily

lu rocyt

eryt

6.2

(If

:uull
esl a

cortisohie

i rig

1 un tue,

1101111:1

hi elevat

wit

of

soar.

67()0 u, 11111). wit hi :1

Si x utli ) s of red (-(115

1951

i 1u(Iisat

I )hysica

I hloracio

hiemoglohlili

hlooal
couiut
was
acidl
i Ii t his 51 oniachu

ansI

I)OSi

olat a shullwsll

cent

suns.

loniplaihuing

posterior

white

1951

sytuilt

servicl

ion

a healed

t Is Ii t was

I hue hatui:t

free

this iusslical

19 pcI

effect

has

have

cells,

101

year

old

white

housewife

decreased
a mediastinal
thymoma.
of

to

tumor

i(

the

maintain

deposition

of

tws)

marrow

Severe

hematopoiet
to

necessary

bone

was

blood

hemosideriui

ago

svideticc

devdlol)e(l
u

(lemonstrate(l

anemia
agents

veais

erythropoiet

of

persisted
or

which
which

sort-isone.

hemoglobin
has

did

on

resection

not

Iransfusioui
at

appeared.

s(v(r(

Pleural

activity.

livable

respond
therapy

levels.

sI i glut

observed.

and

due

nins.
and
hvdlroohiloric

show

platelets

i-ed

a benign

administration

pigmentatiomi

to

associated

appeared

proved

hiornial
hiematocrit

rabls

she

years

failed

been

t en

ansI

alidI

Ii llay

is-I

tob

refiuued
liver
ext rad-t :uud vitamin
B12 by inujest
s-obalt
ous
chloride
by iiiout 11 vi I hout
hettefit

ansi

the

were

differetut

deniolist

ahidi

A 45

Summary:
anemia

has

hout

or

units

pignientation

to

er

has

of

this skin

(:1St

hlistehesl

ve1ut

to

moIst Its later she was again

(elut . She was then
given

two

leukocytes
83

AshiI

Two

heaslachue

from

mImi

reaslnsittssl

mm.,

Septeniber

Ati

oel is were
011 1 lie

of

chsst

milliomu/cu.

46.0
wit

left

rest

removed

again

pallor

between
.

days

the

, ahiol

265,0(X)/cu.
free

was given
crude
liver
extract,

During

tot

cent

was

were
. There

(ells.

fifty-six

also
crude
hier

of 2.9

of

t umor

ohisshalged

she
cough

i ii t he

coutst

of
of

i ye

of

Uhlits

was

of nioderate

adiministered

rose

She

discharge

I)rodlust

findings

iO)hi five

(chit

after

appearaice

ross

t he opdrat

elevated
of

10.--G

Skin

From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

944

BENIGN

Fno.
olle

11 -----1 list

sells
FiG.

whiis:ht
IIr0Ss-til

IX

ologis

s1Ii

IX

scot

i(I1u

(If

\V1TII

t unior

fmoni

olslgic

ssst

ion

nushli- Is-I Is ass

S(X)

frotsi

rigo I

:111:1

o:tse
ti

ihe

c:tse

nio.

2, i llust

155).
loset

te-li

ke

ervthropoiietis

1:11

p:llis:t(li

li

tug of I lie spin-

Ihe

pressiise
and

1:11 i tig

form:lI

of

(Ills

iOllS.

Sc:l

I his liunsdous

are:ss

It dled lymllhiocvt

ilu

ds :tre

)iscissiox

lliluidal,
mtliologis, ahidi hcnmtologic

assistanss,

2. i Ilust

similar.

ANEM1.

I1EFlh.-(TOlIY

600).

12.-- --1 list

t he

lIIYM5IM.

this

ot
anemia

act ivitv

a severs
iii

in the

s-ash
marrow,

features

anemia
case

caused
was

whish

(If our

1)0th

associated
persisted

pat

l)atiehits

with a marked
in spite

strikingly

ate

ictits to
of all

seek

medical

decrease
therapeutic

in

From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

ROSS,

measures.
There
had
were negative
in both

FINCII,

been
cases,

STREET,

AXD

no exposure
and except

to
for

toxic
agents.
the mediastinal

evidence
of other
neoplastic
disease.
The acquired
appeared
to be intercurrent
and was completely
The tumor
removed
from each patient
was
tologic
ment

structure
of the
in the hematologic

patients

have

had

of severe
anemia.
hemochromatosis
The
in our

to be

given

have

acquired

hemolytic

dermoid

cysts

of the

anemia

have

: splenectomy

ovarian

cysts

was

there

death
precluded
the
resection
of a dermoid

was

and

of benign

solitary

without

prompt

possibility
cyst of the

to splenectomy

cases

of benign

patient

(E.

is

tumor

benefit,

T.)

has

associated
at

no time

circulating
erythrocytes.
The refractory
anemias
only

abnormalities

bone

marrow

which

erythroid

to the

in

elements

and

marrow.

No

our

have

these

patients,

and

the

anemias

there
are
by chance
caused

to both.
It is extremely
currence
However,

of a benign
it appears

four
possible
alone,
(2)
the

difficult

to

thymoma
that
the

or (4) that
predict.

the

some

entities
would
be extremely
rare. In view of this
in addition
to the tw-o cases
we have
observed,

L.

the

transient
during

the

platelets
there
has

and

and

depression
was there
a
suspected
of being
factors

therapy

thymomas
that
caused

the

refractory
(3)

factor

the
occurrence

was
of

same

it is of considerable

have

been

various

occurred
anemia,

probability
in

has

with

to
they
the

etiologic

there

the

of

toxic

or
to

anemia
chance

since

patient

known

(1)

of her

for the
L.

hematopoietic

statistical

and refractory
simultaneous

Except

neither

response

other

unusual

patient

Possible

of any

other

Our

hypoplasia

characteristics

considerations:
that
the thymomas

thymomas,

are

leukocytes

in

in the

destruction

marked

iii

erythropoietic
stimulants
has been observed.
In a consideration
of the relationship
of these
anemias,
taneously

anemia
in our
of the hemolytic

anemia.3-

anemia.

no

removal

Postoperative

obtained

patients

been

associated

deficiency

l)y
ovarian

surgical

of increased

been
no evidence
of extramedullary
hematopoiesis.
of the marrow
is believed
to be excluded,
since
history
of exposure
to any
chemical
substance
bone
in

are

were

hemolytic
response
results

thrombocytopenia
and leukopenia
which
developed
episode
of acquired
hemolytic
anemia,
the circulating
have
remained
normal
in number
and morphologic

toxic
to the
demonstrated

anemia
tumors

anemias

anemia.3

hemolytic

evidence

occurred

of the
benign

these

following

of acquired
the excellent

observed

transfusion

accompanied

of

the

recurrence

of

the effects
of splenectomy
and
in the other
case.2 The relation-

acquired

exhibited

consistently

from

contrast
with

no

was

the

specific

tumor

but

recovery

etiology
to find

Two

of observing
spletiic
pedicle

sharp

in

signs

other

recorded.24

of the thymoma
to the appearance
no. 1 (patient
L. L.) is not known,
but

anemia

to prevent

transfusions,

deficiency

been

biopsies

similarity.
No improveof the tumor,
and both

benign
thymoma
and the
interest.
It is uncommon

with
anemia
when
iron
However,
three
instances

node
there

hemolytic
anemia
in case no. 1
relieved
by splenectomy.
a benign
thymoma
and the his-

transfusions
these

Lymph
tumor

considerable
from
removal

numerous

reflection
of
begun
to appear.

As

relationship
between
the
patients
is of considerable

associated
excluded.

ship
case

two tumors
showed
picture
resulted

945

STRIEDER

simul-

chance

oc-

individual.
of these
two
interest-

been

that

common

reported

that,

pre-

From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

946

BENIGN

Case

Ih

1 .-

TAil LE

Opsahl
Hadojevic

Davidsohn

Huniphrevs

Habit

anidl

aludl

Wilutrolle

Chalmers

ANEMIA

A nein ia-lie

poi-ted

Outcome

Sex

Age

Leukocytes
and platelets

1934

56

Decrease

Yes

1935

20

Decrease

No

Death

1941

58

Normal

No

Death

58

Normal

No

Thvnsoma

1945

Myasthenia gravis

Death

1946
Bo-

1953

16

Decrease

45

Norma!

Yes
Yes

ansI

1953

Bo-

62

No

Norma!

Fuste,

ahud

1953

Hosa!es

or aFt

gravis.

This

a hvperplastic

amid

had

Thvmoma

No

anemia

with

pale

marked

Thvmoma

At

atid

died

bands

through

tumor

There

was
for

the

oval,

erythroid
tumor

were

of the
myeloid

was

yellow

suggests

that

firm,

globular,

surface

enclosing

anterior

mediastinum.

network
of polygonal
with
vesicular
nuclei
were
the
with

seen

worth7
female
The

the

and

thymus.

normal
have

encapsulated
smooth,

tumor
homogenous,

hole

picture

was

reported

associated
bone
marrow

the

with a
showed

occurrence
benign

only

of ones

picture.
of epithelial

present

were
of

and
cells
many

uniform

prior to death
elements
with
absence
of
in color.
The clinical
course
it was a benign,
rather
than
marrow

of refractory
anemia
mediastinal
tumor.
At

case

tumor

enclosing
Rudimentary

decrease
elements.

On

areas

w-ith a dark
brown
yellow
nodes
as

compatible

marrow
showed
a definite
myeloid
and
megakaryocytic

The

cells

gradual

size

of metastases

ic nuclei

bone

the

Microscopically

and spindle-shaped
and fat-rich
cytoplasm.

the

cellular

l)ands
Also

hyperchromat

and

marrow

the

with

of

myasthenia

hematologic

corpus(les.

thymus

a case

following

no evidence

the

tissue

of the
w-ith

about

a malignatit,
thymoma.
I)avidsohn,6
in 1941, reported
a
in
a 58 year
old female
in association
with an upper
autopsy
sectioned
the upper

resecteol

reported

male

interspersed

description

the
the

a firm

Hassels

eel ls w-ith
of

of

old

to account

Histologic

description

year

chest.

resembling

autopsy

a 56

organs

ret icular
nu(lei.

Opsahl

iii

cdl

unchahugedl

tumor

1934

of fibrous
about

and

of a 1)enign

1). In

autopsy

anterior

hypoplasia

histologic

resect
unchanged

thynsonia.

paticytopema
At

upper

no

instatices

(table

a severe

Scattered

in palisades
polygonal

megakaryocytes.
and

No

Normal

but

other

aplastic

in the

of nerosis.

showed

45

anemia

marrov
or to other
tumor
consisted

and

Normal

I hynius,

us seven

to

the

arranged
irregular,

44

of agranulo(ytosis.

to bone

size

lund

found

rssectesi
cured!

Auuensia

patient

development

areas

1953

refractory

carciuioma

as

Thymoma

Anemia

known

thymic

sectioii

1953

Street,

associated

fist

No

St risdsr

11:11 ient

viously

with

Normal

improved

Anemia

Street,

Finch.
llull

This

47

St rieder

Ross,

Fillet),

:ttid
10

resscted

Aliemia

Chediak,
Hoss,

improved

Thvnsoma

hseimer

resected

Anemia

Chalmers

cured

Thvmotna

hei nier
7

resecteol

Anemia
Deal ii

F
and

Cases

I)ate

Southworth
5*

REFRA(TORY

00(1 Refractory

ynsona

Author

WITII

TIIYMOM.-t

with
in

as

lobulated
found
in

composed

of

groups
of large
cells
Hassels
corpuscles
a lymphoepithelioma
red cell precursors
Humphreys
and

of
along
South-

of a refractory
anemia
in a 58 year
old
epithelial
tumor
of the anterior
mediastinum.
mild
hypoplasia
of the erythroid
elements.

From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

FIN(iI,

ROSS,

Following
rapidly

surgical
to normal.

degenerated
At autopsy
Hahn5

one

corpuscles,

year

reported

was

Chalmers
rhage

all

performed

pleura
was

locally
followed

and

in five

in a short

the

again,
before

and the
operation.

which

had

evidence
Chalmers
and have

of relapse

elements

of

peripheral

of anemia
agreed

and

to allow

in

relapsing.

doses
again

a further

has

as well

tumor,

invaded

the

all
vith

to

but

gravis

he-

as the

operation

the

mediast.inal

of the tumor
bone marrow

peripheral

blood,

they

dropped

and
to nil

which
existed
his myasthenia

Splenectomy
was later
of ACTH.
Favorable
reoc(urred
which
lasted
for

course

of ACTH

followed

w-as given.

and

appeared

been

now

aiid

respond

the erythroid
aplasia
spleen
enlarged
and

large
blood

showed

a thymoma,

weeks

also

and

values.

to 1)e treated

a similar

three

hemor-

biopsy

to

reveal

of

leukocytic

had

which

than

or myasthenia
have

not

reticulocytes

He

marrow-

patient.

myasthenia

of malignancy.
Removal
red cell precursors
of the

was
with

treatment

with

differential

failed

appeared

occurred

Boheimer9

kindly

in

although

with

In less

operation

erythrohlasts.

and

and

normochromic

amid myasthenia

regressed
to
the patients

and

Bone

the
did

reticulocytes

again
of ACTH

day

numerous

Radojevic

evidence

and

anemia

atid

signs
of the

cent.

total

thymoma

combined

marrow

Relapse

The

association

in

no other
to normal

with
as

its

studies.

chest

a large

first

this

of bone

three
weeks.
On the sixth

of

(ells.

pancytopenia

male
and

precursors,

thymoma

of

bone
marrow
Subsequently

and

like

cellular

without

normocyti(

in

cell

of the

to 20 per

improved

performed

both

ACTH

revealed

rose

were

normal.

x-rays

but showed
by a return
days

the

old

anemia

numerous

connectioti
of anemia

and

time

and

that

a 48 year

cells

red

including

know-n
cases

%vas

showed

on
were

Repeated

cause
of the
rare
reported

red

normal

absent

hematinics

transfusions.

found.

tumor

thought

observed

His

elements

available

as

lymphocyte

fibrous
tumor
of the thymus
gland
and
was found.
Prior
to death
x-ray
therapy

a profound

recognizable

megakaryocytic

sponse

have

was

were
of

aiid

tumor

thymic

it svas

and

developed

count

Heti(ulocytes

tumor

disease.

cell

absence

of any

of a benign

Boheimert

suddenly

white

evidence

cells,

picture
as restored
origin
and consisted

destroyed.

or hemolytic

his

the

beets

and

who

gravis

no

At autopsy
a cystic
of the bone marrow
to

had

947

STR1EDER

spindle-shaped

occurrence

old male.
hypoplasia

tumor

later

the

administered

the

AND

resection
of this tumor
the hematologic
The tumor
appeared
to be of thymic

Hassels

20 year
extreme

STREET,

the

for one

marrow

year

without

gravis.

a second
us to (ite it here.

observed

patient
with
This
patient,

this syndrome
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

tumor,
followed
ten

days

marrow
that

benefit.

A large

a thymoma
the operation
reticulocytes
which

appeared

previously

this remission
Chediak,
Fuste,

mediastinal

tumor

was
removed.
l)ut she again
had

was

demonstrated

Slight
transient
relapsed.
After

and

numerous

shown

no

would also be transient.

and Rosales#{176} report

erythroblasts
erythroblastic

the

case

by

x-ray

the

and

hematologic
improvement
100 mg. of ACTH
a day
were

present

elements.
of a 47

year

It
old

for
the

in

appeared

white

male

From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

948

BENIGN

with

profound

TIIYMOMA

normocyti(

WITH

anemia

REFRA(TORY

and

complete

elements
of the bone
marrow. The
leukocytes
granulopoietic
and
megakaryocytic
elements
Multiple
hematinic
agents
vere ineffective
fusions

were

strated

radiographically,

thymoma.

necessary.

anterior

All

and

Reticulocytes

aplasia

was

appeared

in

mediast-inal

removed

the

in

of the

erythropoietic

and platelets
of the blood
and
of the
marrow
were
normal.
relieving
the anemia,
amid tratis-

superior

this

ANEMIA

tumor

surgically

blood

twenty-four

was

proved

to

hours

after

operation

and increased
marrow
and
Wintrobe

to 18 per cent on the sixth

the peripheral
blood
returned
mentions
in his textbook,

day. Red sell elements

appeared
to normal
and remained
so.

information

oti,1

myasthenia

gravis

pancytopenia

of

duration

-ho

after

heeii

hematocrit

as

per

old

developed

having

60

a 16 year

(chit

girl

purpura

treated

and

with

guanidine

died

its

The

mi(roscopic

not

cytic

elements.

presence

structure
This

as

case

gland,

All seven

of these

patients

had

our own two patients,

poietic
and megakaryocytic
almost

decrease
in
granulopoietic
died, whereas
It

remarkable

and
only

benign

gland

on

subject
of the

the

tumors

ill

in

with

the

treated

with

hemorrhagicum
complete
absence
limits

of normal
in lympho-

here,

and

of the
way

of thymic

origin

of our
In four

of the blood
were normal
In

two

related

to

which

appear

was

the

They
anemia
as well

and
cases,

and granuloeven
though

patients

a marked

thymomas

it is not

medication

patients.

marrow,

and

normal.

ere

there

was

reduction

in the marrow.
Both
leukocytes
amid platelets

of these

with

lobulation

with those
the bone
transfusion.

blood,

elements
normal

The

to 3600,

was

reported

of erythropoiesis.

presence

normal
during

chni(al

gland

the

have

related

body,

hut

occurs,

evidence

However,

function.

shrouded

there
is some
be physiologically

involuted

l)est

others

months

months.

for an increase

and platelets
of the marrow

platelets

megakaryocytic
one of those

remains

observations
hand,
may

absence
and

that

of their

thymus

system

1700

upper

and

additional

origin

five

corpus
with

a
in

these
patients
succumbed.

responsible

for

the

of the refractory
amiemias.
In most
endocrine
glands
(i.e. thyroid,
adrenal,
parathyroid,
amid islets
of Langerhans),
hyperplasia
or
change
induces
metahohc
disturbances
which
usually
represent
some

alteration
this

for

at the

except

to the

leukocytes
elements

complete

leukocytes

is possible

appearance
hypophysis,
neoplastic

as

consisten(y,

is dissimilar

in

was

prostigmine

which

color,

with

undetermined

or not the hypoplasia

of the marrow
-a.s a result
had beeti given,
or was idiopathic,
or was in some
the enlarged
thymus
gland.

of

there

us

he
in the

of fourteen

30,000,
and leukocytes
was stopped
and
she

to be similar
(although
perhaps
not identical)
all had
decreased
erythropoietic
activity
refractory
to all therapeutic
measures
except
as

provided

seven
months
later
of ruptured
lie
bone marrow
was hypoplastic

of megakaryocytes.
The thymus
for this age,3 weighed
38 Cm. ;

clear vhether
the patient

has

and

22 pet cent,
platelets
lymphocytes.
Guanidine

transfusions
but
and
hemoperitoneum.

and

with

demon-

and

in

past

mystery

forty

thymi(
tione

evidence
active.
many

in

years.

function

of these

the
spite
Many

to

reports-

have

that
the atrophic
While
much
fatty
foci

for a systemic

of

thymic

effect

normal
of well

function

over

clinical

2000
amid

disturbances
been

of

confirmed.

of the adult
publications
experimental

almost
On

every
the

other

appearing
thymus
of the adult
and fibrous
replacement
of the
and

of the

syncytial

hyperplastic

cells

thymus

remain.ti

gland

The

is

in

From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

ROSS,

myasthenia
over

gravis

a period

amsimals
resection

where

of years

STREET,

thymectomy

have

to

It would

have

circulating
in most

heels

of considerable

The

Other
experiments
by
spontaneous
leukemia

thymie
plete

atrophy
surgical

of the

gland

in

cortisomse,
of the

(which

is not

such

had

the

incidence

suggest

that

some

system,

although

Climiical
thymic

for

more
thymus.

evidence

a thymic

of

altered

to

thymus

glatid

the

patiemsts

and

the

have

a continuing

possibility

must
adverse

as to the possible
beneficial
exert
on our patietsts
atsd
The

third

for

possibility

the
was
he

by

the
causative
by

years
t-hymic

before
tumors

the

isot

evidence

removed

case

comssidered
on

the

hematopoietic

no.

betw-eemi
in which

improvemeist
or
by resection

refractory

the
the

Isot

defimmite.

time

the

tumor

of the thymus
of refractory
anemias

may

in cure
of the

etiologic

but

relatiomi-

In
was

that
persistemice
of thymic
erythropoiesis.
It is interesting

effect
that
removal
On certain
other
cases

re-

studies

the developmemst
of anemia,
of the cases of Humphreys,7

supporting

at the

its
its

These

relatiomsship
our

not

is suggestive,

retaits

effective

amsd the

in

were

was

commatrix

is obscure.

relieved

that

tumors

by

may

mice.

iii

patient-s

itifluemsce

is that

also

Chediak#{176} resulted

anemia

patiemits

cortisone)

thymus

a possible
three

but
the
criticism.

24

that
although
inhibit-ion
producitig
lymphoid
and

leukemia

betweems

of the

in
or
its

investigators
ere able
to
stock
of mice
from
80.8

development.
thymectomy

relatiomsship

be coticluded

thymoma

of our

23,

imshibitioms
sas obtaitsed
suggests
that
the reticular

is provided

Boheimer,#{176} amid
In comstrast
our

It must
the

These
leukemic

of this

erythropoiesis

known
to exist
fact that removal

Chalmers
and
the anemia.

26

effective
This

exist

isature

supporting

and

of

thymoma.

does

effects

the hematopoietic
svstem
rio extracts
were prepared.
influetice
omi hematopoiesis
is

Unfortumsately,

sigisificamstly

exact

investigators

on

carcinogen-imiduced

relatioms
the

tumor

tumor
was
amid by the

ship

of

Mamsy
hematopoiet-ic

of thymic
extracts
consisted
of changes

extracts

extracts

capacity
to allow
or to promote
leukemia
Kirschbaum
amsd Falls28
report
that
ducing

various

and Furth27
itidicated
mice
was obtaimsed
by

T.ptoti

with
removal

palliative.5

and
erythrocytes,#{176}20,
are subject
to cotisiderable

provided
by the studies
of Furth,
et al.25
reduce
the incidemice
of leukemia
in a high
per cent to 9.9 per cemit by thymectomy.
of

be

the administratioms
observations
have

imsterest

amid the effect

of
by in vivo
experiments.
best
experimemstal
evidemice

evaluated

STRIEDER

ascribe

leukocytesm622
of these
studies

prepared

949

AND

may

attempted

and human
subjects
to either
of the thymus
gland.
These

the msumber
of
results
obtained
been

FINCH,

two

tissue
may
to speculate

glatid
anemia.
have

our

resected,

itself

might.

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
Furthermore,
of the anemia
A
is that
atrophic
response

possible

which
might
be responsible
the presetice
of the tumor
in at least one case.
explanations

for

the

they
both
have
1)een produced
thymus
glamsd may
rapidly
to adremsalectomy,
castratioms,

for

is known

simultaneous

the

development
to antedate
occurrence

the
of

of the tumors.
developmemst

these

disorders

by a commomi
etiologic
factor.
The adult
assume
its maximal
prepuheral
size its
hypophysectomy,
partial
thyroidect-omy,

From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

950

TIIYMOMA

tiENIGN

Addisomss

hypert-hyroidism,
and

imsfectioms.29

hormomses,

#{176}

stress,

which

have

derivatives
particularly

the

regulators.

have

this

of

profoumid

The

amid

important
and

steroid
agemits
been
the
beets
amid!

hematopoietic

the
are

I 1-17

principal
have

atiemias
all

oxysteroids

of

strikimsg

hypoclitsical

appear

of circulating
gratiulocytes,
apparemit
effect
of these

ots

of

cholamithretse
has
vari()us
hormones,

hypothyroidism

iisfiuemice.

the
msuml)er
reticulocytes.
The

The
atsemia

he

disease

allergy,

iisfluence

31

refractory

to

inactivity,

the

drugs.29

showts

amid

drugs,

under

that
methyl
More
receistly

of Cushiisgs

disease,

hormone

effect

eositsophils,

beets

polycythemia

Addisotis

examples

it is interesting
hyperplasia.32

steroi(ls

The

pituitarism,

o(cur

and certain
a cause
of

as

ANEMIA

changes,

may

chaisge,

iti(rimiiiated

ISEF1SACTOSSY

dietary

atrophy

of henzol,
atid
produce
thymic

to

showts

disease,

Rapid

dietary

beets

\VITtI

to

have

lymphocytes,
steroids
oti
both

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

the

amid

Irrespective

good

evidemice

related.

amsemia

of

the

that

pattern,

or as

visualized

surgical

in

Boheimers

radiologic

imi patiemits

case,

and
refractory

wit-h

of erythropoietic

actual

study.
of the

resection

exploration

combitiatioti

occurretsce

of disorders,

amid that

they

careful
study
or refractory

there

are

is

etiologically

of the
anemia

thymus
amsd
is observed.

is not
overtly
enlarged
its cases
of refractory
anemia
it is
may
he siglsificamst
deviatioms
from
the msormal
histologic

by

followed

which

utiusual

a (hamsce

it is justifiable
to recommend
whemsever
either
thymoma

bomse marrow

Eveis
if the thymus
possible
that
there
l)e

of this

it is not

Therefore

of the

is utsktsowms.

etiology

thymoma

In view
thymoma

iti

possibly
of resectioms
anemia,
particularly

elemetsts

of the

boise

may

of the

marked

three

1)e present
clitiical

cases

which
catimsot
improvement

the

of the thymus
those
with

advisability

of

should
be comisidered
hypoplasia
or aplasia

marrow.

SUMMARY

1. The

simultamseous

which
failed
beets observed
2.

Reports

amid refractory

to

occurretice

respomsd

its two
of

to

adult

seven

with

female

other

anemia

of a betsigis

therapy

summarized.
3. Possible
explatsations
conditions
are discussed.

amid a severe

hematopoietic

anemia
has

agetits

patiemsts.

patients

have

t-hymoma

recognized

beets

with

foumsd

atsd

similar

the

associatioms

,saliemst

of

features

thymoma

of these

oases

are

4.

It

etiologically

is suggested
responsible

of the

that

the
for

simultamseous

thymus
certaits

SUMMARIO

I. Ha essite observate
de tin thymoma
benigne
le agentes
hematopoietic

in duo
e un

adulte
sever

normalmente

occurrence

glaisd

or

tumors

cases

of refractory

IN

INTERLINGUA

patientes
anemia

feminin
que

empleate.

non

of these
of the

two

thymus

ummusual
may

he

atsemia.

le occurrentia
respondeva

simultanee
a! therapia

con

From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

ROSS,

2. On
refractori

ha

trovate
esseva

FINCH,

reportos
similemente

STREET,

AND

5TRIEDER

de septe
altere
patientes
associate.
Le tractos

951

in qui
saliente

thymoma
de iste

e anemia
casos
es

summarisate

3. Possibile
explicationes
inusual
es discutite.

del

occurrentia

4. Es considerate
le possibilitate
logicamente
responsahile
pro certe

simultanee

que
casos

le thymo
de anemia

de

iste

o tumores
refractori.

duo

del

conditiones

thymo

es etio-

REFERENCES
t

POPE,

R.

H.

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BENIGN

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#{176}MCENDY,

gonads

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From www.bloodjournal.org by guest on September 3, 2015. For personal use only.

1954 9: 935-952

The Simultaneous Occurrence of Benign Thymoma and Refractory Anemia

JOSEPH F. ROSS, STUART C. FINCH, RUSSELL B. STREET, JR. and JOHN W. STRIEDER

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