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Malignant lymphoma in a patient with relapsing bronchiolitis obliterans organizing pneumonia. S Romero, C Martín, B Massutí, I Aranda and L Hernandez Chest 1992;102;1895-1897 DOI 10.1378/chest.102.6.1895 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/102/6/1895
Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright1992by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692
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may involve an indirect effect of ischemia evoked by the
posed to severe O@desaturation.
Bezold-Jarisch
COPD, it is serious and potentially lethal, since their O@
paradoxical
reflex.
In the
bradycardia
present
case,
however,
the
is hard to explain only by impair
transport
is impaired
to various
In those patients degrees
due
with
to decreased
ment of coronary perfusion, since an angiographic study
02 uptake
revealed
should be kept in mind when one sees patients such as those with COPD who are potentially exposed to acute hypoxemia due to an exacerbation of the underlying disease.
normal
blood
supplies
to all branches
and
no
ischemic ECG changes were observed, not only during hypoxic patient
challenge but also during exercise. Therefore, this was different from the case documented in the
in the
lung.
Therefore,
exercise
or progressive
hypoxia
was an initial
O@, the same phenomenon
was still observed
to
some extent, despite sufficient systemic oxygenation. Thus, a regional tissue hypoxia around the SA node, which is disproportionately severe compared with systemic hypoxe mia, is most likely to be responsible
for the paradoxical
bradycardia in this case. It may reflect the direct inhibitory action of hypoxia on cardiac pacemaker activity that has
been shown experimentally in other species2 or indirect effect of hypoxia mediated through such mechanisms as local production of adenosine.@ Exercise-induced coronary spasms in the absence
of fixed organic stenosis
may be
involved, although this alone cannot entirely explain the observed hypoxic
phenomenon, challenge
since it was also evidenced
without
during
exercise.
In general, the SA node activity is continuously modulated by afferent inputs from various peripheral receptors. The indirect effect ofhypoxiaon the SA node function is mediated through humans,
interactions of several opposing influences. In the stimulation of carotid bodies usually causes
cardiac slowing,@which effect is modulated by adverse cardioacceleration
receptor hypoxic
mediated
through
(PSR) stimulated exposure,
the
pulmonary
rate
usually
During
accelerates
if
ventilation is allowed to increase, since PSR activation overrides the direct effect of carotid bodies. Aortic chemo receptors probably hypoxic exposure, humans.6
contribute to cardioacceleration although they may play a minor
during role in
The carotid body function of the present case must be intact, since he showed a good ventilatory hypoxic
challenge.
Thus,
decreased
exercise,
relationship
to a mid-right
artery
stenosis.
2 MarshallJM, MetcalfeJD. Analysis ofthe cardiovascular changes induced in the rat by graded levels ofsystemic hypoxia. J Physiol 1988; 407:385-403 3 Belardinelli L, Linden J, Berne RM. The cardiac effects of adenosine. Proc Cardiovasc Dis 1989; 32:73-97 4 Daily M DeB, Scott MJ. The effects of stimulation of the carotid body chemoreceptors on the heart rate ofthe dog. J Physiol 1958; 144:148-66 5 Gross PM, Whipp BJ, Davidson J1@Koyal SN, Wasserman K.
Role of the carotid bodies in the heart rate response to breath holding in man. J AppI Physiol 1976; 41:336-40 6 Karim F, Hainsworth R, Sofola OA, Wood LM. Responses of the
heart to stimulation of aortic body chemoreceptors in dogs. Circ Res 1980;46:77-83 7 Heistad DD, Abboud FM, Mark AL, Schmidt PG. Effect of baroreceptor activity on ventilatory response to chemoreceptor stimulation. J Appl Physiol 1975; 39:411-16
MalignantLymphomain a Patient withRelapsingBronchiolitis ObliteransOrganizingPneumonia* Santiago Romero, M.D.; Concepcion Martin, M.D.;
Bartomeu Massuti, M.D.; ignaclo Aranda, M.D.; and LasLcHernandez,
M.D.
A case of relapsing
bronchiolitis
of the
obliterans
organizing
pneumonia complicated by malignantlymphoma (four years after the diagnosis) is reported in a 58-year-old woman. To our knowledge, such an association has not been described previously in detail in the literature.
response during
efficacy
coronary
Chest 1988; 94:407-08
stretch
by hyperventi1ation.@
heart
phenomenon
1 MillerTD, Gibbons RJ. Paradoxical heart rate deceleration during
increase and then a sudden deceleration at a point when Sa02 fell below 85 percent or 90 percent. While inhaling 100 percent
unique
REFERENCES
recent report.' The pattern of his heart rate changes during incremental
this
(Chest 1992; 102:1895-97)
PSR
mediated reflex due to emphysema, decreased activities of the aortic bodies due to chronic hypoxemia, and hyperre activity of the carotid bodies specific to the heart rate response may also have been involved in the cause of the
BOOP = bronchiolitis obliterans organizing pneumonia; CHOP = cyclophosphamide, doxorubicin, vincristine, and prednisone; EBV= Epstein-Barr virus; HTLV human T-cell
lymphotropic virus; NHLnon-Hodgkin's transbronchial
lymphoma; ThB
biopsy
bradycardia. A marked increase in arterial blood pressure as a consequence contribute
of hypoxemia
to an additional
slowing
and severe dyspnea through
arterial
may
barore
ceptor stimulation.@However, the observed response seems difficult to explain only by these neural mechanisms. First, at least in the initial course of both exercise and HVR tests, there was a gradual cardioacceleration; second, vagal cardiac reflexes reflected in respiratory sinus rate fluctuation or the sinus response to atropine infusion were fairly good; and third, the heart rate steadily increased in parallel with ventilation during the hypercapnic challenge. Regardless of the mechanisms involved, the paradoxical cardiodeceleration in response to hypoxia must be clinically
quite disadvantageous, particularly when subjects are ex
@ronchm1itis obliterans
organizing
pneumonia
(BOOP)
is
a clinicopathologic entity in which intraluminal fibrosis of distal airspaces etiology
is often
is the major pathologic unknown.l
As
in other
feature.
The
cryptogenetic
disorders, multiple associated conditions have been men
tioned. Although coexistent lymphoma has been reported,a we were unable to find a previous complete description of this association. The patient whose case is reported herein suffered from both conditions over a six-year period. *Fmm the Secciónes de Neumologla
(Drs. Romero, MartIn, and
Hernandez) y Oncologla (Dr. Massuti) y Servicio de Anatomia Patologica
(Dr. Aranda),
Hospital
General
S.V.S. , Universidad
de
Alicante, Alicante, Spain. CHEST I 102 I 6 1 DECEMBER, 1992
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1895
@
@&
•1@f@@
CASE REPORT A .58-year-old previously fit woman experienced nonproductive cough, fd\'VI@, and progressive dvspnea three weeks before the first admission to the hospital (August 1984). Physical examination revealed
ii,ild obesity
acid l)ihasilar
inspiratory
sounds were normal . No lymphadenopathy
crackles;
the heart
was found . The hemo
globin @@‘uts 12 g/dl; the white l)l(xx1cell count was 21,600/cu mm (79 Percent neutrophils). There was no eosmnophilia.The erythro cyte sedii,wiitatioi@ rate wues)X) mon/h . The chest roentgenograms
showed (liffilse, patch@ linear, and alveolar opacities throughout both lungs. PaO, was 67 mm 11g. PaCO2 was 35 mm Hg, and pH was 7.44 (Flu.,
0.21). The \‘Cwas 1.15 L (37 percent
of predicted)
and the FE@, was 0.9 L (42 Percent of predicted). Erythromycin 500 tug four times daily for two weeks resulted in no symptomatic improvement, and a chest roentgenogram showed increased shad owing (Fig 1). Examination with a flexible bronchoscope revealed (liffllse ilOlell
iliflanimatory silOVI'e(l
filling
loose connective blasts.
The findings
changes.
A transhronchial
of alveolar
and
tissue containing were
consistent
biopsy
bronchiolar
lumina
inflammatory
(TBB) spec h@' buds
of
original magnification
cells and fibro
with a diagnosis
of BOOP
X 200).
(Fig mesenteric
area.
Serologic
studies
for Epstein-Barr
virus
(EBV)
2). Microbial infections were excluded by special stains and cultures of coincident specimens aIld there wa.s no evidence of neoplasia. Treatment with prednisone 60 tug/day was started. There was rapid
and human T-cell lymphotrophic virus (HTLV) were negative. A chemotherapy regimen based on cyclophosphamide, doxoruhicin,
symptomatic
vincristine, and prednisone (CHOP) was administered during the
and radiologic
improvement
with virtual
resolution
of
shadowing after OHU months treatment. The dose of prednisone was taiwred and later discontinued after 13 months. Two new symptolilatic and roentgenographic relapses (March 1986 and October 1987) rapidly improved when steroid therapy was reintro duced. In December 1988, when she was again receiving a dose of prednisone
of 10 nig every
other
da@ she felt a lump
in the neck,
aoid physical examination confirmed the presence ofenlarged lymph nodes, 1 to 2.5 cm in size, in the left supraclavicular and axillary regions. I listologic exalnlination of cervical l@'mph node biopsy
specimens revealed a complete effacement ofthe nodal architecture l)@'a ll()dular, diffuse proliferation of small and intermediate lym phoid cells with cleaved and noncleaved nuclei (Fig 3). These findings were consistent with the diagnosis ofmalignant lymphorna,
diffuse mixed, small and large cells of intermediate grade of malignanc@@ill the working formulation.' At this time, the patient had no respiratory synflptonls, a chest roentgenogram showed fl()
@
FIGURE 2. Transhronchial biopsy specimen demonstrating polypoid plugs of fibroblastic tissue filling air space (hematoxylmn-eosin,
infiltrates, and VC was 107 percent of predicted. A tomographic
((::‘r) scan showed an additional
computed
site of disease in the
following five months, achieving complete clinical remission from the sixth week. In August 1990, cough and dyspnea once again appeared, a chest roentgenogram showed an infiltrate in the lingula, and after demonstrating by TBB lesions consistent with BOOP, prednisone treatment was restarted with striking response. Ten months later, the patient is still receiving prednisone at a dose of 20 mg every other day and is free of ostensible disease. DISCUSSION BOOP may be due to a variety of causes, including inhalation of toxic gases, connective tissue disorders, infec tion, and bone marrow and heart-lung transplantation. 1.2,4In most cases of BOOP, however, no cause is found.' As many as two thirds of the patients with BOOP demonstrate complete clinical and physiologic recovery following prednisone therapy, but in some patients, as in ours, a dose of 10 to 20 mg every other day may be required Open
lung biopsy
specimens
have been
considered
the
S
I
FIGURE 3. Cervical
Fu;t'RE 1. Posteroanterior chest roentgenogram patchy infiltrates throughout both lungs. 1896
showing diffuse
li-mph
node biopsy
specimen
showing
diffuse
lymphoma with large and small cleaved cells. Note small lymphoid cells with angular or cleaved nuclei and large cells with prominent nucleoli (hematoxvlin-eosin, original magnification x 200). MalignantLymphoma in Patient with Relapsing BOOP (Romero et a!)
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gold standard for diagnosis of BOOP Some authors argue that TBB is inadequate for diagnosis because of the small specimens obtained and the patchy nature of the disease.' Nevertheless,
as has been
shown previously,
good transbron
chial specimens in conjunction with an appropriate clinical context may be adequate to establish a clinical diagnosis of
BOOP.5°Moreover, as in recipients of heart-lung trans plants,@'@ TBB may offer a safe and repeatable method to
207:382-94
6 Bartter T, Irwin RS, Nash G, BalikianJP, HollingsworthHH. Idiopathic peripheral
bronchiolitis obliterans organizing pneumonia with infiltrates on chest roentgenogram. Arch Intern Med
1989; 149:273-79 7 Higenbottam T, Stewart S, Penketh A, Wallwork J. Transbron chial lung biopsy for the diagnosis
of rejection
in heart-lung
transplant patients. Transplantation 1988; 46:532-39 8 Yousem SA, Paradis IL, Dauber
JH, Griffith
B? Efficacy of
obtain tissue for histologic study from patients with BOOP
transbronchial lung biopsy in the diagnosis of bronchiolitis
and a relapsing course, as the one whose case was reported
obliterans in heart-lung transplant recipients.
herein. When our patient presented
1989; 47:893-95
a lingular infiltrate after
the diagnosis of lymphoma had been established, we were forced to confirm its true nature histologically, since both conditions, BOOP and non-Hodgkin@slymphoma (NHL), share the roentgenographic alveolar opacities. NHL infiltration in the absence
(5.5 percent
appearance of multiple patchy
rarely presents of involvement
with pulmonary outside the chest
as initial site), but in case of relapse,
is mention made of two patients in whom lymphoma coexisted with bronchiolitis obliterans.° Both cases had . added pathologic conditions: diabetes in one and idiopathic
thrombocytopenic purpura in the other. Additional infor mation on these cases is scanty, and neither the type of bronchiolitis nor its cause can be determined from the report. Whether a true pathogenic relationship exists between
these two infrequent diseases remains to be defined. The role of corticosteroids
in our patient
must be considered. Although the relationship between the use ofother immunosuppressive agents such as cyclosporine and the development of NHL have been demonstrated, such a link has not been observed with 10On the other hand, these agents may facilitate infection by viruses
with oncogenic
properties,
giant cells nor intranuclear
but neither
multinucleate
predispose
Clarkson BD. The non-Hodgkin@slymphomas, I: a retrospective clinical and pathologic analysis of499 cases diagnosed between
1958 and 1969. Cancer 1983; 51:101-09
10 Keown PA, Stiller CR. Cyclosporine:a double edged sword. Hosp Pract 1987; 22:207-20
ReversibleLeft Ventricular DysfunctionInducedby Recurrent VentricularTachycardia* Kanji Iga, M.D.; Kenjim Hori, M.D.; and Tadashi Matsumura, M.D., F.C.C.P
Two cases of transient LV dysfunction associated with VT are described. Both patients had a history of palpitations of several years' duration without symptoms of congestive heart failure. The reason for presentation was an increase in frequency and duration of palpitation. Decreased LV wall motion, observed by 2DE, normalized shortly after treatment of the VT Diffusely decreased LV wall motion is associated with frequent episodes of VT and may mimic
DCM except that signs and symptoms of heart failure are
absent.
(Chest 1992; 102:1897-98)
inclusions typical of viral infec
tion were noted in our patient. Genetic and acquired immune deficiency and autoimmune disorders
9 Straus DJ, Filippa DA, Lieherman PH, KozinerB, Thaler HT,
with
postmortem study this figure may increase to 37.8 percent.9 To the best ofour knowledge, in only one previous article
immunosuppressive
Transplantation
to the development
oflymphoid
malig
2DE = two-dimensionalechocardiography; DCM dilated car diomyopathy;
%FS
fractional
shortening;
LVleft
ventricu
lar; LVDd LV end-diastolic dimension; LVDs LV end-sys tolic dimension; VT ventricular tachycardia
nant neoplasms. The dramatic response of BOOP to corticosteroids'
and the association
of BOOP with both
connective tissue diseases and organ transplantation provide circumstantial support for an autoimmune pathogenesis. In our patient, a single autoimmune mechanism cannot be excluded.
S evere
myocardial
impairment
which
1985; 312:152-58
2 GosinkBB, Friedman PJ, LiebowAA. Bronchiolitisobliterans: roentgenologic-pathologic correlation. AJR 1973; 117:816-32 3 National Cancer Institute. National Cancer Institute sponsored study of classffication of non-Hodgkin@s lymphomas: summary and description of a working formulation for clinical usage. Cancer 1982;49:2112-35
4 Muller NL, Staples CA, Miller RE. Bronchiolitis obliterans CT features
normalized
CASE
1 Epler GR, Colby T@ Mcloud TC, Carrington CB, Gaensler EA. Bronchiolitis obliterans organizing pneumonia. N Engl J Med
in 14 patients.
AJR 1990;
5 Davison AG, Heard WA, McAllister WAC, Turner-Warwick MEH. Cryptogenic organizing pneumonitis. Q J Med 1983;
associated
with VT has a poor
shortly
after
treatment
of
frequent episodes of VT.
REFERENCES
organizing pneumonia: 154:983-87
disease
prognosis.We present two cases with LV wall motion
CASE
REPORTS
1
A 41-year-old man had a history of transient rapid palpitations for several years. The palpitations became more frequent and severe, lasting for more than 24 h, and he presented to our outpatient department two days after one such episode. He had not received any medication for arrhythmia. Two-dimensional echocar diography showed diffusely decreased LV motion at a time when the patient had normal sinus rhythm. Left ventricular end-diastolic
and end-systolic dimensions were 45 and 37 mm, respectively (Fig 1, top left). The patient was treated with verapamil, 120 mg/day, *From the Department
of Cardiology, Tenn Hospital, Tenri City,
Japan. Reprint requests: Dt iga, DepartmentofCardiology,
Tenri Hospital,
Tenri 632, Japan CHEST I 102 I 6 I DECEMBER, 1992
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1897
Malignant lymphoma in a patient with relapsing bronchiolitis obliterans organizing pneumonia. S Romero, C Martín, B Massutí, I Aranda and L Hernandez Chest 1992;102; 1895-1897 DOI 10.1378/chest.102.6.1895 This information is current as of July 10, 2011 Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/102/6/1895 Cited Bys This article has been cited by 5 HighWire-hosted articles: http://chestjournal.chestpubs.org/content/102/6/1895#related-urls Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.chestpubs.org/site/misc/reprints.xhtml Reprints Information about ordering reprints can be found online: http://www.chestpubs.org/site/misc/reprints.xhtml Citation Alerts Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to the right of the online article. Images in PowerPoint format Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online figure for directions.
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