bronchiolitis obliterans organizing pneumonia ...

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 SecciÃ³nes 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


1895

@

@&

â€¢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 @@â€˜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 \â€˜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

((::â€˜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!)


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.5Â°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.Â° 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


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.
