CASE REPORT
published: 24 May 2021
doi: 10.3389/ med.2021.627004
F on ie s in Medicine | www. on ie sin.o g 1May 2021 | Volume 8 | A icle 627004
Edi ed by:
Ca l Kie an O ,
Sain Vincen ’s Uni e si y
Hospi al, I eland
Re iewed by:
Ga i allia Sakella iou,
Uni e si y o Pa ia, I aly
Paul S udenic,
Medical Uni e si y o Vienna, Aus ia
*Co espondence:
Manuel Sil é io-An ónio
[email p o ec ed]
Special y sec ion:
This a icle was submi ed o
Rheuma ology,
a sec ion o he jou nal
F on ie s in Medicine
Recei ed: 07 No embe 2020
Accep ed: 21 Ap il 2021
Published: 24 May 2021
Ci a ion:
Sil é io-An ónio M, Pa la o F,
Ma ins P, Khmelinskii N, B az S,
Fonseca JE and Polido-Pe ei a J
(2021) Gas ic Adenoca cinoma
P esen ing as a Rheuma oid Fac o
and An i-cyclic Ci ullina ed P o ein
An ibody-Posi i e Polya h i is: A Case
Repo and Re iew o Li e a u e.
F on . Med. 8:627004.
doi: 10.3389/ med.2021.627004
Gas ic Adenoca cinoma P esen ing
as a Rheuma oid Fac o and
An i-cyclic Ci ullina ed P o ein
An ibody-Posi i e Polya h i is: A
Case Repo and Re iew o Li e a u e
Manuel Sil é io-An ónio1,2*, Fede ica Pa la o3, Pa ícia Ma ins1,2, Niki a Khmelinskii1,2,
Sand a B az3, João Eu ico Fonseca1,2 and Joaquim Polido-Pe ei a1,2
1Rheuma ology Depa men , Hospi al de San a Ma ia, Cen o Hospi ala Uni e si á io Lisboa No e, Lisbon Academic
Medical Cen e, Lisbon, Po ugal, 2Rheuma ology Resea ch Uni , Faculdade de Medicina, Ins i u o de Medicina Molecula ,
Uni e sidade de Lisboa, Lisbon, Po ugal, 3Medicina 2 Depa men , Uni e si y Hospi al Cen e o Lisbon No h, Lisbon,
Po ugal
A 64-yea -old male p esen ed wi h a 6-mon h his o y o symme ic polya h i is in ol ing
p oximal in e phalangeal join s and me aca pophalangeal join s o he hands, w is s, and
ankles. Associa ed symp oms included omi ing, p og essi e a igue, and weigh loss.
Labo a o y esul s showed mic ocy ic anemia, leukocy osis, h ombocy osis, ele a ed
C- eac i e p o ein and e y h ocy e sedimen a ion a e, and heuma oid ac o (RF) and
an i-cyclic ci ullina ed p o ein (ACPA) an ibody posi i i y. Join s adiog aphs we e no mal,
wi hou e osions. Uppe endoscopy and gas ic endoscopic ul asonog aphy showed
a gas ic adenoca cinoma wi h lympha ic in ol emen . In aope a i ely, pe i oneal
ca cinoma osis was documen ed, and he pa ien s a ed pallia i e chemo he apy.
A pa aneoplas ic se oposi i e a h i is was assumed, and ea men wi h low-dose
p ednisolone and hyd oxychlo oquine was s a ed. A h i is emission was achie ed
and sus ained up o 18 mon hs o ollow-up, al hough gas ic cance p og ession was
documen ed. We desc ibe a unique pheno ype o pa aneoplas ic a h i is (PA) p esen ing
as a se oposi i e (RF and ACPA posi i i y) heuma oid a h i is (RA) wi h a good esponse
o bo h low dose co icos e oids and hyd oxychlo oquine he apy. We also e iew he
li e a u e o PA, mos ly he RA-like pa e n, and he associa ion be ween PA and ACPA
posi i i y. This case highligh s he impo ance o conside ing unde lying cance in elde ly
male pa ien s, p esen ing wi h polya h i is and sys emic symp oms, e en in hose wi h
ACPA-posi i e RA-like a h i is.
Keywo ds: pa aneoplas ic synd ome, pa aneoplas ic a h i is, se oposi i e a h i is, heuma oid a h i is, gas ic
cance
INTRODUCTION
Pa aneoplas ic synd omes a e mani es a ions o a malignan disease ha a e no di ec ly caused by
he umo i sel and occu dis an om he p ima y umo o me as asis. Tempo al ela ionship
is he main c i ical issue o iden i y pa aneoplas ic synd omes, and as a ule, he mani es a ions
mus occu du ing a malignan disease o p ecede i by no longe han 2 yea s (1–3). The bes
Sil é io-An ónio e al. Gas ic Adenoca cinoma P esen ing as Se oposi i e Polya h i is
e idence o he associa ion be ween he clinical mani es a ions
and he malignan disease is es ablished e ospec i ely when he
symp oms imp o e o comple ely emi wi h he ea men o
he unde lining neoplasm (1,2). A spec um o heuma ologic
mani es a ions can esul om a pa aneoplas ic p ocess and
a e p esen in abou 7–10% o pa ien s wi h cance , including
a h i is, lupus-like synd omes, in lamma o y myopa hies,
asculi is, and hype ophic os eoa h opa hy (1,3–5).
Pa aneoplas ic a h i is (PA) can p esen simila ly o o he
in lamma o y a h i is, and some ea u es a e used o dis inguish
i om hose diseases. I a ec s mo e o en elde ly men
(male/ emale a io o 1.7:1 and a median age o onse o 54 yea s)
and was classically desc ibed as a se onega i e and non-e osi e
asymme ical oligo-polya h i is in ol ing mos equen ly he
knees, ankles, w is s, and hands (5–7). Recen ly, a symme ic
polya h i is indis inguishable om heuma oid a h i is (RA) as
a p esen ing ea u e o PA has been documen ed, and isola ed
case epo s o PA wi h heuma oid ac o (RF) and/o an i-
cyclic ci ullina ed pep ide an ibody (ACPA) posi i i y ha e been
published (4,8–11). These da a sugges ha a h i is’ pa e n
and se ology may no be en i ely eliable in he iden i ica ion
o possible cases o PA (4). In his case-based e iew, we
epo a gas ic adenoca cinoma p esen ing as RA wi h RF and
ACPA posi i i y, and we e iew he li e a u e o PA, mos ly he
se oposi i e pa e n.
CASE REPORT
A 64-yea -old male p esen ed o he eme gency depa men
wi h a 6-mon h his o y o g adual onse o join pain, swelling,
and mo ning s i ness in ol ing he w is s, me aca pophalangeal
(MCP) join s, p oximal in e phalangeal (PIP) join s, and ankles.
In addi ion, he complained o occasional omi ing, ano exia,
p og essi e a igue, and unin en ional 12 kg o weigh loss. His
a h algia was p og essi e and debili a ing, and had a poo
esponse o non-s e oidal an i-in lamma o y d ugs (NSAIDs),
ace aminophen, and opioid analgesics ( amadol 200 mg daily).
His pas medical his o y and medica ion we e i ele an
besides being an ex-smoke (10 pack-yea s, s opped 10 yea s
ago). He had a amily his o y o gas oin es inal and pulmona y
malignancies. He denied any o al ulce s, d y eyes, ash, e e ,
nigh swea s, gas oin es inal bleeding, o o he complain s. On
physical examina ion, a h i is o he w is s, MCP join s, PIP
join s, and ankles, and a posi i e me a a sal squeeze es we e
no ed. The es o he examina ion was un ema kable.
The ini ial labo a o y in es iga ions unco e ed a mic ocy ic
and hypoch omic anemia (hemoglobin 7.9 g/dl), leukocy osis
(12.7 ×109/L), h ombocy osis (904 ×109/L), and ele a ion
o C- eac i e p o ein (CRP; 17.3 mg/dl) and e y h ocy e
sedimen a ion a e (ESR; 94 mm/h). Renal and li e p o iles
we e no mal, and an in ec ion sc een was nega i e. An
anemia in es iga ion showed low se um i on (9.6 µg/dl)
and ans e in sa u a ion (4%), and no mal e i in (74.1
ng/dl), cyanocobalamin (465 pg/ml), and ola e (5 ng/ml)
le els. Radiog aphic e alua ion o he a ec ed join s and
ches was un ema kable. The RF and ACPA we e signi ican ly
FIGURE 1 | Gas ic mass on (A) uppe gas oin es inal endoscopy and (B)
abdomen compu ed omog aphy ( ed a ow).
ele a ed a 215 IU/ml (0–14 IU/ml) and 156.9 IU/ml (<20
IU/ml), espec i ely.
Uppe gas oin es inal endoscopy exhibi ed on he lesse
cu a u e and an um o he s omach a ha d and iable
mass wi h a eas o nec osis ha condi ioned luminal s enosis
(Figu e 1A). Endoscopy ul asound o he uppe gas oin es inal
ac e ealed a mass ex ending 17 mm o he se osa laye
wi h egional in ol emen o ou lymph nodes. Endoscopy
biopsy specimens showed a gas ic adenoca cinoma wi h
poo di e en ia ion. Con as -enhanced ches –abdomen–pel is
compu ed omog aphy con i med he gas ic mass wi h no
e idence o o he adenopa hy o dis an me as asis (Figu e 1B),
and he umo was a ed T3N2M0, G3. Ches e alua ion showed
sligh changes compa ible wi h emphysema.
Du ing he hospi aliza ion, while he malignancy wo kou
was ongoing, polya h i is was ea ed wi h a sho cou se o
co icos e oids (dexame hasone 5 mg daily) wi h good clinical
esponse, and he dose was quickly ape ed. Howe e , a ew
weeks la e , his symp oms ecu ed, and he was eadmi ed
due o se e e polya h i is wi h disabling gai . Co icos e oid
he apy was ein oduced (p ednisolone 20 mg daily), and
F on ie s in Medicine | www. on ie sin.o g 2May 2021 | Volume 8 | A icle 627004
Sil é io-An ónio e al. Gas ic Adenoca cinoma P esen ing as Se oposi i e Polya h i is
FIGURE 2 | Timeline disease ac i i y o a h i is and ela ion wi h chemo he apy d ugs, co icos e oids, and hyd oxychlo oquine. DAS28 3 -PCR, Disease Ac i i y
Sco e o 28 join s wi h h ee a iables ( ende join coun , swollen join coun , and C- eac i e p o ein); DEXA, dexame hasone; HCQ, hyd oxychlo oquine; PDN,
p ednisolone.
hyd oxychlo oquine (200 mg daily) was also added. Howe e ,
ull adhe ence o he he apeu ic egimen was only possible
a e a ew mon hs and only hen was a comple e esolu ion o
polya h i is achie ed (Figu e 2).
He was e e ed o oncology and p oposed o gas ec omy.
Du ing he lapa o omy p ocedu e, ex ensi e pe i oneal
ca cinoma osis was de ec ed, whe eby he unde wen
gas ojejunos omy. The pa ien s a ed pallia i e chemo he apy
wi h cispla in and luo ou acil, and a e HER2 o e exp ession
was documen ed, as uzumab was added. Cispla in and
luo ou acil we e s opped a e 8 mon hs, bu cance p og ession
was documen ed and we e ein oduced la e on, wi h li le e ec
on a h i is con ol. A e 18 mon hs o ollow-up, he emained
ali e, wi h sus ained a h i is emission o o e 9 mon hs
(documen ed clinically and using ul asound) and wi hou
adiological de ec able e osions, unde ea men wi h low-dose
p ednisolone (<7.5 mg daily) and hyd oxychlo oquine (300 mg
daily), despi e he absence o a cu a i e cance ea men .
DISCUSSION
O e all, pa ien s wi h RA a e a an inc eased isk o cance
compa ed wi h he gene al popula ion. Howe e , gas ic cance
has a lowe incidence in RA pa ien s, which can be explained
by he inc eased use o NSAIDs in his popula ion (12–15). The
incidence o RA in pa ien s wi h gas ic cance is no known.
A wide a ie y o solid and hema ological malignancies has
been associa ed wi h PA, wi h lung adenoca cinoma being he
TABLE 1 | T adi ional cha ac e is ics o pa aneoplas ic a h i is [adap ed om
S umm oll e al. (5), La son e al. (8), Caldwell and McCallum (19), and
P i zenmeye e al. (20)].
1. Close empo al ela ionship (12 mon hs) be ween he
onse o a h i is and malignancy
2. Olde age
3. Join in ol emen in an asymme ic dis ibu ion
4. P edominance o lowe ex emi y in ol emen
5. Explosi e onse
6. Absence o amily his o y o heuma ic disease
7. Absence o heuma oid nodules
8. Absence o cha ac e is ic adiog aphic lesions o RA
9. Absence o RF
10. Non-speci ic his opa hologic appea ance o he
syno ial lining
RA, heuma oid a h i is; RF, heuma oid ac o .
mos equen (3,9). Thus, a , only ou pa ien s wi h PA we e
epo ed ha ing gas ic umo s, none wi h a se oposi i e RA-like
pa e n (3,16–18).
Based on he e iew o case epo s, PA was adi ionally
desc ibed as a se onega i e asymme ic oligoa h i is wi h
p edominan in ol emen o he lowe limb join s (Table 1).
Howe e , a symme ic polya h i is indis inguishable om RA is
now ecognized o be he mos equen pa e n, in a ew cases
associa ed wi h RF o ACPA.
F on ie s in Medicine | www. on ie sin.o g 3May 2021 | Volume 8 | A icle 627004
Sil é io-An ónio e al. Gas ic Adenoca cinoma P esen ing as Se oposi i e Polya h i is
TABLE 2 | New cha ac e is ic ea u es p oposed o he diagnosis o
pa aneoplas ic a h i is [adap ed om Mo el e al. (3)].
1. A e age ime be ween a h i is and neoplasia diagnosis <6 mon hs
2. Men age >50 yea s
3. Polya h i is (symme ic o asymme ic)
4. Absence o heuma oid nodules
5. Absence o e osions on adiog aphy
6. Absence o RF
7. Deg ada ion o gene al heal h s a us
8. High CRP le el
9. Reg ession o a h i is a e speci ic an i- umo al he apy
CRP, C- eac i e p o ein; RF, heuma oid ac o .
Classic PA ea u es we e de ailed by Kisacik e al. (7) by
compa ing pa ien s wi h PA (n=65) wi h pa ien s diagnosed
wi h ea ly RA (n=50). In his s udy, he PA g oup was de ined by
using p e iously desc ibed adi ional ea u es, and he inclusion
c i e ia we e apid disease onse and symme ic o asymme ic
disease mos ly a ec ing he lowe ex emi ies and usually spa ing
he small join s o he hands. Consequen ly, pa ien s wi h RA-like
a h i is we e excluded om he PA g oup, which o igina ed an
unin en ional bias in he desc ip ion o PA cha ac e is ics.
An ea lie s udy by Mo el e al. be e cha ac e ized his
ype o a h i is, in a case se ies o 26 pa ien s wi h PA, using
a less es ic i e a h i is pa e n—oligo-polya h i is e ol ing
o a maximum o 2 yea s be o e cance diagnosis (3). Despi e
con i ming mos o he adi ional ea u es, such as he absence
o RF and adiologic lesions, hey concluded ha he majo i y o
pa ien s displayed ea u es o RA, being symme ic polya h i is,
in ol ing w is s and hands, he mos equen a icula pa e n
(85%). The e o e, hey p oposed a new g oup o cha ac e is ic
ea u es o he diagnosis o PA (Table 2).
A e iew by Wa son e al. also included se e al pa ien s wi h
PA wi h symme ic dis ibu ion and in ol emen o he w is s,
small join s o he hands, and knees, esembling RA. Con a y o
p e ious epo s, some o hese pa ien s we e posi i e o bo h RF
and ACPA (9).
Ou pa ien p esen ed wi h an RA-like pa e n and high
i e o bo h RF and ACPA mee ing he 2010 Ame ican
College o Rheuma ology/Eu opean League Agains Rheuma ism
classi ica ion c i e ia o RA. To he bes o ou knowledge, his
is he six h case desc ibed in he li e a u e classi iable as a PA
wi h RF and ACPA posi i i y (Table 3). O in e es , ou o hese
pa ien s also had an RA-like pa e n, wi h e osi e a h i is p esen
in one o hem. Mos o he pa ien s esponded well o low-
dose co icos e oid he apy, bu due o he ad anced s age o
he malignancies, umo he apy was cu a i e in a single pa ien ,
and only in his case, a comple e esolu ion o he PA occu ed.
None o he epo ed cases men ions he p esc ip ion o disease-
modi ying an i- heuma ic d ugs (DMARDs), which may be
explained by he concomi an chemo he apy o p edic able poo
gene al condi ion o a pa ien wi h ad anced neoplas ic disease.
Despi e he ac ha PA was classically desc ibed as e ac o y
o co icos e oids and NSAIDs, he s udy by Mo el e al. showed
some con adic o y in o ma ion. NSAIDs and co icos e oids
we e e ec i e, espec i ely, in 45 and 91% o he pa ien s, bu
wi hou ob aining a sus ained emission. DMARDs (sul asalazine
and me ho exa e) we e only e ec i e in one ou o i e
ea ed pa ien s.
Two s udies analyzed a se ies o pa ien s wi h pa aneoplas ic
heuma ologic synd omes and showed ha he majo i y o PA
we e ACPA nega i e (7,21). ACPA ha e simila sensi i i y as
RF o RA bu wi h a highe speci ici y (90–95%), hus, allowing
mo e accu a e diagnosis o RA, especially in cases o ea ly
undi e en ia ed a h i is (8,9). Howe e , his es is no 100%
speci ic, and ACPA posi i i y has been epo ed in a a ie y
o diseases (21–25). As his case highligh s, he p esence o
ACPA in he con ex o a polya h i is should no exclude
au oma ically o he diagnos ic en i ies, pa icula ly in elde ly
pa ien s wi h consump i e symp oms. O e looking his migh
delay he diagnosis and ea men o unde lying cance (8,9).
ACPAs a e o med agains ci ullina ed an igens ha
appea a e enzyme-ca alyzed pep ide ans o ma ion by
pep idyla ginine deiminase (PAD) enzymes. In RA, hese
an igens a e ound in in lamma o y syno ial memb anes, and
ACPAs ha e been shown o pe pe ua e join in lamma ion and
co ela e wi h mo e agg essi e disease (26). In hema ological
and solid umo s, PAD enzymes a e up egula ed and ha e been
implica ed in he ca cinogenesis p ocess (27). In 2014, Handy
e al. p oposed a possible associa ion be ween ACPA posi i i y
and PA (4). They sugges ed ha ACPA could appea due o
he o e exp ession o PAD enzymes in malignan diseases,
gene a ing ci ullina ed pep ides, which a e hen exposed o he
immune sys em. Howe e , his hypo hesis does no explain all
PA cases (as mos a e ACPA nega i e) no o e s a comple e
mechanis ic elucida ion o he PA phenomena.
In he p esen case, he onse o a symme ic polya h i is in an
elde ly man, associa ed wi h cons i u ional symp oms and i on
de iciency anemia led us o an addi ional wo kup. In ou opinion,
he cha ac e is ic ea u es p oposed by Mo el e al. (3) (Table 2)
a e mo e ep esen a i e o he ull spec um o PA and should be
p e e ed in clinical p ac ice.
Cance p og ession was seen in ou pa ien and was
accompanied by la es o polya h i is, despi e ongoing
chemo he apy. We should no e ha some chemo he apy d ugs
can imp o e RA clinical mani es a ions, namely, cispla in and
luo ou acil, which we e used in his pa ien (28,29). Howe e ,
in his case, chemo he apy d ugs did only ha e a modes e ec ,
and a h i is emission was only possible when ull adhe ence
o hyd oxychlo oquine and p ednisolone was achie ed. Since
he e ec o hyd oxychlo oquine in mono he apy in RA is qui e
modes when compa ed wi h o he classic DMARDs, especially
in double se oposi i e RA, i is p obable ha in ou pa ien ,
he a h i is emission was achie ed due o he combina ion o
hyd oxychlo oquine, p ednisolone, and chemo he apy (30).
Acco dingly, we belie e ou case ep esen s a se oposi i e PA,
being he i s case ela ed o gas ic malignancy. Un o una ely,
he s aging o ou pa ien s’ malignan disease de e mined
pallia i e su ge y and chemo he apy, and he likelihood o
cu a i e ea men is e y low. We canno , hus, conclude i
a h i is would emi wi h he ea men o unde lying cance .
F on ie s in Medicine | www. on ie sin.o g 4May 2021 | Volume 8 | A icle 627004
Sil é io-An ónio e al. Gas ic Adenoca cinoma P esen ing as Se oposi i e Polya h i is
TABLE 3 | Cha ac e is ic ea u es o published cases o RF and ACPA-posi i e pa aneoplas ic a h i is.
Re e ence Age/sex Type o
malignancy
Du a ion o
symp oms
p eceding
cance
diagnosis
(mon hs)
Family
his o y o
cance
A h i is loca ion
and pa e n
Onse Anemia ESR
(mm/h)/
CPR
(mg/dl)
RF (IU/ml)
/ACPA
(IU/ml)
Join
adiog aphs
Response
o NSAIDs
Response
o
co icos e oids
Cance
ea men
used
( esponse o
e olu ion)
Kuma e al.
(11)
58/M Panc ea ic cance 2 N.M. No a h i is; a h algia
in ol ing hands, w is s,
elbows, shoulde s,
lowe back, and neck;
asymme ic and
in e mi en
G adual Yes ++/N.M. + + +/++ N.E. N.M. Yes None (died)
Raja e al.
(10)
40/M Lymphoma oid
g anuloma osis
3–4 No W is s, knees, and
ankles; symme ic
G adual No –/+ ++/++ N.E. N.M. Yes (pa ial) None (died)
La son e al.
(8)
45/F Lung
adenoca cinoma
3 No PIP, MCP, elbows, and
knees; symme ic
N.M. No –/+ ++/+N.E. No Yes (pa ial) None (died)
Handy e al.
(4)
61/F T cell
lymphoblas ic
leukemia
1–2 No MCP, w is s, knees,
and ankles; symme ic
Acu e Yes + + +/++ + + +/++ E osions No No Hype -CVAD
CMT
( e ac o y)
Wa son e
al. (9)
80/F B eas papilla y
cance
1 N.M. Shoulde a h i is;
a h algia in ol ing
w is s, shoulde s, and
knees; asymme ic and
mig a o y
Acu e Yes –/++ +/+N.E. No Yes CMT (N.M)
and RT
( emission)
P esen
case
64/M Gas ic
adenoca cinoma
6 Yes (GI and
lung)
PIP, MCP, w is s, and
ankles; symme ic
G adual Yes ++/+ + + ++/++ N.E. No Yes 5-FU and CIS
CMT (no
cu a i e)
CPR, C- eac i e p o ein; ESR, e y h ocy e sedimen a ion a e; ACPA, an i-cyclic ci ullina ed pep ide an ibodies; RF, heuma oid ac o ; NSAIDs, non-s e oidal an i-in lamma o y d ugs; F, emale; M, male; GI, gas oin es inal; MCP,
me aca pophalangeal join s; PIP, p oximal in e phalangeal join s; 5-FU, luo ou acil; CIS, cispla in; hype CVAD, cyclophosphamide, inc is ine, doxo ubicin, and dexame hasone; CMT, chemo he apy; RT, adio he apy; N.E., no e osions;
N.M., no men ioned.
ESR: – i <30, +i ≥30, and <60, ++ i ≥60 and <100, +++i ≥100.
CPR: +i ≥0.5 and <5.0, ++ i ≥5.0 and <15.0, +++i ≥15.0.
RF i e : +i ≥14 and <100, ++ i ≥100 and <300, + + + i ≥300.
ACPA: +i ≥20 and <100, ++ i ≥100 and <300, +++i ≥300.
F on ie s in Medicine | www. on ie sin.o g 5May 2021 | Volume 8 | A icle 627004

Sil é io-An ónio e al. Gas ic Adenoca cinoma P esen ing as Se oposi i e Polya h i is
In conclusion, ou case illus a es ha physicians
should be awa e and ule ou cance in an ACPA-
posi i e RA-like polya h i is in pa ien s wi h
cons i u ional symp oms and/o wi h labo a o y
ea u es showing se e e anemia, h ombocy osis, and
e y high CRP.
DATA AVAILABILITY STATEMENT
The o iginal con ibu ions p esen ed in he
s udy a e included in he a icle/supplemen a y
ma e ial, u he inqui ies can be di ec ed o he
co esponding au ho /s.
ETHICS STATEMENT
E hical e iew and app o al was no equi ed o he s udy on
human pa icipan s in acco dance wi h he local legisla ion and
ins i u ional equi emen s. The pa ien s/pa icipan s p o ided
hei w i en in o med consen o pa icipa e in his s udy.
AUTHOR CONTRIBUTIONS
MS-A con ibu ed o he manusc ip concep ion, design, and
li e a u e e iew. MS-A, FP, PM, NK, SB, JF, and JP-P con ibu ed
o he manusc ip p epa a ion and c i ical e iew. All au ho s
ha e ead and app o ed he inal e sion o he manusc ip .
REFERENCES
1. Mange B, Sche G. Rheuma ic pa aneoplas ic synd omes – a clinical
link be ween malignancy and au oimmuni y. Clin Immunol. (2018) 186:67–
70. doi: 10.1016/j.clim.2017.07.021
2. Doll R. Si aus in b ad o d hill, 1897–1991. S a Med. (1993) 12:795–
808. doi: 10.1002/sim.4780120808
3. Mo el J, Deschamps V, Toussi o E, Pe uise E, So de C, Kie e P, e al.
Cha ac e is ics and su i al o 26 pa ien s wi h pa aneoplas ic a h i is. Ann
Rheum Dis. (2008) 67:244–7. doi: 10.1136/a d.2007.070086
4. Handy CE, Robles G, Haque U, Hous on B. T cell ALL p esen ing as
se oposi i e heuma oid a h i is: case epo and e iew o he li e a u e
on se oposi i e pa aneoplas ic a h i is. Clin Rheuma ol. (2015) 34:1647–
50. doi: 10.1007/s10067-014-2697-9
5. S umm oll GH, A inge M, Machold KP, Smolen JS, Rade e M. Cance
polya h i is esembling heuma oid a h i is as a i s sign o hidden
neoplasms: epo o wo cases and e iew o he li e a u e. Scand J Rheuma ol.
(2001) 30:40–4. doi: 10.1080/030097401750065319
6. Hashe i M. The ela ionship be ween heuma ologic diso de s
and malignancies. Rheum Dis Clin No h Am. (2018) 44:405–
18. doi: 10.1016/j. dc.2018.03.003
7. Kisacik B, Ona AM, Kasi oglu T, Pehli an Y, Pamuk ON, Dalkilic E, e al.
Diagnos ic dilemma o pa aneoplas ic a h i is: case se ies. In J Rheum Dis.
(2014) 17:640–5. doi: 10.1111/1756-185X.12277
8. La son E, E wa u D, Si a C, Lawlo K. Repo o an i-CCP an ibody posi i e
pa aneoplas ic polya h i is and e iew o he li e a u e. Rheuma ol In . (2011)
31:1635–8. doi: 10.1007/s00296-009-1294-8
9. Wa son GA, O’Neill L, Law R, McCa hy G, Veale D. Mig a ing polya h i is
as a ea u e o occul malignancy: 2 case epo s and a e iew o he li e a u e.
Case Rep Oncol Med. (2015) 2015:934039. doi: 10.1155/2015/934039
10. Raja R, Lamon D, Yung A, Solanki K. A can o ed he ings:
an i-CCP posi i i y in lymphoma. In J Rheuma Dis. (2010) 13:e46–
50. doi: 10.1111/j.1756-185X.2010.01535.x
11. Kuma S, Se hi S, I ani F, Bode BY. An icyclic ci ullina ed pep ide an ibody-
posi i e pa aneoplas ic polya h i is in a pa ien wi h me as a ic panc ea ic
cance . Am J Med Sci. (2009) 338:511–2. doi: 10.1097/MAJ.0b013e3181b0babe
12. Chang SH, Pa k JK, Lee YJ, Yang JA, Lee EY, Song YW, e al.
Compa ison o cance incidence among pa ien s wi h heuma ic
disease: a e ospec i e coho s udy. A h i is Res The . (2014)
16:428. doi: 10.1186/s13075-014-0428-x
13. Wil on KM, Ma eson EL. Malignancy incidence, managemen , and
p e en ion in pa ien s wi h heuma oid a h i is. Rheuma ol The . (2017)
4:333–47. doi: 10.1007/s40744-017-0064-4
14. Wu CY, Wu MS, Kuo KN, Wang CB, Chen YJ, Lin JT. E ec i e educ ion
o gas ic cance isk wi h egula use o nons e oidal an i-in lamma o y
d ugs in Helicobac e pylo i-in ec ed pa ien s. J Clin Oncol. (2010) 28:2952–
7. doi: 10.1200/JCO.2009.26.0695
15. Wong BCY, Zhang L, Ma J, Pan K, Li J, Shen L, e al. E ec s o selec i e COX-2
inhibi o and Helicobac e pylo i e adica ion on p ecance ous gas ic lesions.
Gu . (2012) 61:812–8. doi: 10.1136/gu jnl-2011-300154
16. Chaun H, Robinson CE, Su he land WH, Dunn WL. Polya h i is associa ed
wi h gas ic ca cinoma. Can Med Assoc J. (1984) 131:909–11.
17. Enomo o M, Takemu a H, Suzuki M, Yuha a T, Akama T, Yamane K,
e al. Palma ascii is and polya h i is associa ed wi h gas ic ca cinoma.
Comple e esolu ion a e o al gas ec omy. In e n Med. (2000) 39:754–
7. doi: 10.2169/in e nalmedicine.39.754
18. Rabah S, Bani Hani D, Jilani N. Pa aneoplas ic a h i is in a pa ien wi h gas ic
cance : a case epo . Cu eus 12:e9692. doi: 10.7759/cu eus.9692
19. Caldwell DS, McCallum RM. Rheuma ologic mani es a ions o cance . Med
Clin No h Am. (1986) 70:385–417. doi: 10.1016/S0025-7125(16)30960-9
20. P i zenmeye P, Biele eld Ph, Ta e nie Ch, Besanceno JF, Gaude M. Aspec s
ac uels de la polya h i e aiguë pa anéoplasique. La Re Méd In e . (1992)
13:195–9. doi: 10.1016/S0248-8663(05)81326-8
21. Wen J, Ouyang H, Yang R, Bo L, Zhang Y, Tang M, e al. Malignancy
domina ed wi h heuma ic mani es a ions: a e ospec i e single-cen e
analysis. Sci Rep. (2018) 8:1786. doi: 10.1038/s41598-018-20167-w
22. Londhey V, Shah MM. An i CCP an ibodies in ube culosis. J Assoc Physicians
India. (2016) 64:26–8.
23. Romic Z, De ek L, Bu ek V, Unic A, Se da T, Ma ijance ic D, e al. An i-
cyclic ci ullina ed pep ide and heuma oid ac o in HIV posi i e pa ien s.
Rheuma ol In . (2011) 31:1607–10. doi: 10.1007/s00296-010-1539-6
24. Ruiz-Esquide V, Góma a MJ, Peinado VI, Gómez Pue a JA, Ba be á JA,
Cañe e J de D, e al. An i-ci ullina ed pep ide an ibodies in he se um
o hea y smoke s wi hou heuma oid a h i is. A di e en ial e ec o
ch onic obs uc i e pulmona y disease? Clin Rheuma ol. (2012) 31:1047–
50. doi: 10.1007/s10067-012-1971-y
25. Du Toi R, Whi elaw D, Taljaa d JJ, du Plessis L, Esse M. Lack
o speci ici y o an icyclic ci ullina ed pep ide an ibodies in ad anced
human immunode iciency i us in ec ion. J Rheuma ol. (2011) 38:1055–
60. doi: 10.3899/j heum.100713
26. De ksen VFAM, Huizinga TWJ, an de Woude D. The ole o au oan ibodies
in he pa hophysiology o heuma oid a h i is. Semin Immunopa hol. (2017)
39:437–46. doi: 10.1007/s00281-017-0627-z
27. Chang X, Han J, Pang L, Zhao Y, Yang Y, Shen Z. Inc eased PADI4 exp ession
in blood and issues o pa ien s wi h malignan umo s. BMC Cance . (2009)
9:40. doi: 10.1186/1471-2407-9-40
28. Sanchez-Bu son J, Apa icio LA, Mendez M, Galdo F. cis-pla inum, a
ea men o e ac o y heuma oid a h i is? B J Rheuma ol. (1989)
28:358. doi: 10.1093/ heuma ology/28.4.358
29. Bunch TW, E lichman C, Lu h a HS, Ma eson EL. An open-label, phase
I/II s udy o 5- luo ou acil plus leuco o in in he ea men o heuma oid
a h i is. J Rheuma ol. (2002) 29:1109–10.
30. Smolen JS, Landewé RBM, Bijlsma JWJ, Bu mes e GR, Dougados M,
Ke schbaume A, e al. EULAR ecommenda ions o he managemen
F on ie s in Medicine | www. on ie sin.o g 6May 2021 | Volume 8 | A icle 627004
Sil é io-An ónio e al. Gas ic Adenoca cinoma P esen ing as Se oposi i e Polya h i is
o heuma oid a h i is wi h syn he ic and biological disease-modi ying
an i heuma ic d ugs: 2019 upda e. Ann Rheum Dis. (2020) 79:685–
99. doi: 10.1136/ann heumdis-2019-216655
Con lic o In e es : The au ho s decla e ha he esea ch was conduc ed in he
absence o any comme cial o inancial ela ionships ha could be cons ued as a
po en ial con lic o in e es .
Copy igh © 2021 Sil é io-An ónio, Pa la o, Ma ins, Khmelinskii, B az, Fonseca
and Polido-Pe ei a. This is an open-access a icle dis ibu ed unde he e ms
o he C ea i e Commons A ibu ion License (CC BY). The use, dis ibu ion o
ep oduc ion in o he o ums is pe mi ed, p o ided he o iginal au ho (s) and he
copy igh owne (s) a e c edi ed and ha he o iginal publica ion in his jou nal
is ci ed, in acco dance wi h accep ed academic p ac ice. No use, dis ibu ion o
ep oduc ion is pe mi ed which does no comply wi h hese e ms.
F on ie s in Medicine | www. on ie sin.o g 7May 2021 | Volume 8 | A icle 627004