(Chest. 1999;115:1207-1210.)
© 1999
American College of Chest Physicians
Pulmonary Intravascular Lymphomatosis*
Presentation with Dyspnea and Air Trapping
Jeffrey G. Walls, MD;
Y. Gia Hong, MD;
Joseph E. Cox, MD;
Kevin M. McCabe, MD;
Kevin E. O'Brien, MD;
Jeffrey P. Allerton, MD and
Stephen Derdak, DO, FCCP
*
From the Departments of Pulmonary/Critical Care (Drs. Walls and Derdak), Hematology/Oncology (Drs. Hong and Allerton), Radiology (Dr. Cox), Pathology (Dr. McCabe), and Internal Medicine (Dr. O'Brien) Wilford Hall, USAF Medical Center, Lackland AFB, San Antonio, TX.
Correspondence to: Jeffrey G. Walls, MD, Captain, USAF, MC, 2200 Berquist Dr., Suite 1, Wilford Hall Medical Center, Department of Pulmonary/Critical Care Medicine/MMCP, Lackland AFB, TX 78236
 |
Abstract
|
|---|
Intravascular lymphomatosis (IVL) is a rare lymphoid
neoplasm that is typically of B-cell lineage and characterized by
proliferation of malignant cells within small arterioles, capillaries,
and venules. We report a patient with pulmonary IVL who presented
clinically with progressive dyspnea, fever, and a dry cough. Pulmonary
function tests revealed a marked decrease in diffusion capacity with
airflow obstruction and severe air trapping. High-resolution CT (HRCT)
of the chest with inspiratory and expiratory images revealed mosaic
attenuation consistent with air trapping. Transbronchial biopsies
revealed the diagnosis of IVL with capillary expansion in the alveolar
and peribronchiolar interstitial tissue. IVL should be considered in
the differential diagnosis of a patient with an interstitial lung
disease, air trapping on pulmonary function tests, and mosaic
attenuation on HRCT. Transbronchial biopsies may be the initial
diagnostic procedure of choice.
Key Words: air trapping • high-resolution CT • intravascular lymphomatosis • mosaic perfusion
|
Introduction
|
|---|
Intravascular lymphomatosis
(IVL)
is a rare lymphoma that usually originates from B-cells and has a
predilection for the lumen of small blood vessels. Clinical symptoms
occur when the malignant cells proliferate within the vasculature and
eventually compromise blood flow. Typical sites of involvement
with lymphoma such as the lymph nodes, bone marrow, and solid organs
are usually spared in IVL. The syndrome was first described in
1959,1
and dermatologic and neurologic symptoms dominate
the clinical presentations of the case reports and series that have
been reported to date.2
3
4
5
There have, however, been case
reports that describe a predominant involvement of the
lungs.5
6
7
8
9
10
In these cases, the diagnosis is frequently
difficult to make antemortem because the clinical and radiographic
findings are often nonspecific. This report describes the first case,
to our knowledge, of IVL that presented with evidence of air trapping
on pulmonary function tests and a mosaic attenuation pattern on
high-resolution CT (HRCT) of the chest.
|
Case Report
|
|---|
A 63-year-old man who had quit smoking 30 years previously,
presented with a 3-month history of progressive dyspnea on exertion,
1-month history of a dry nonproductive cough, intermittent-fevers as
high as 40°C, night sweats, and an 8.6-kg (19-lb) weight loss
from his baseline of 80 kg. Dyspnea progressed to the point of
breathlessness after 100 yards of ambulation. Two courses of oral
antibiotics for presumed bronchitis did not improve his symptoms. There
was no prior history of lung disease or occupational dust exposure.
Physical examination revealed faint bibasilar crackles but no
adenopathy, skin changes, peripheral edema, dementia, or focal
neurologic deficit.
Laboratory findings included normal electrolytes and renal function
with a creatinine of 1.0 mg/dL, BUN of 15 mg/dL, and an unremarkable
urinalysis. The CBC revealed a hemoglobin of 12.0 g/dL, hematocrit of
34.8%, and a WBC count of 5,100. The erythrocyte sedimentation rate
was 102 mm/h. The serum lactate dehydrogenase (LDH) was 1,825 U/L
(normal, 105 to 233 U/L) associated with an elevated aspartate
transaminase of 124 U/L (normal, 0 to 37 U/L). The total bilirubin,
alanine transaminase, and haptoglobin were normal. The evaluation for
rheumatic disease was unremarkable, including negative results for
rheumatoid factor, antinuclear antibodies, and C- and P-antineutrophil
cytoplasmic antibodies. The purified protein derivative with the
anergy panel revealed the patient to be anergic. A bone marrow biopsy
and aspiration did not reveal any malignancy or diagnostic abnormality.
Pulmonary function tests were performed, revealing an FVC of 2.96 L
(75% predicted), an FEV1 of 1.81 L (60%
predicted), and an FEV1/FVC ratio of 61%, which
are consistent with moderately severe airflow obstruction. Total lung
capacity was 9.22 L (148% predicted) with a residual volume of 6.42 L
(280% predicted). The diffusion capacity was 5.35 mL/min/mm Hg (20%
predicted).
The initial chest radiograph revealed mild hyperinflation with linear
opacities in the medial lung bases bilaterally. On the lateral view,
the left hemidiaphragm was silhouetted in the posterior sulcus with a
patchy opacity. A chest CT was ordered to further characterize the
infiltrate, and it showed the left lower lobe area to contain a linear
stranding density. A patchy bilateral mosaic pattern was observed, and
the hila and mediastinum contained no significant adenopathy. An
abdominal and pelvic CT revealed only splenomegaly with a craniocaudal
dimension of 15 cm and several subcentimeter hypodensities within the
spleen. All other organs appeared normal, and no retroperitoneal,
pelvic, or inguinal adenopathy was noted.
An HRCT was obtained to evaluate the mosaic attenuation seen on
conventional CT. The initial inspiratory HRCT revealed heterogeneous
lung opacity in a patchy or mosaic distribution (Fig 1
, top, A). This mosaic attenuation or "mosaic
perfusion"11
pattern was thought to be secondary to air
trapping. This was confirmed by the expiratory HRCT (Fig 1
,
bottom, B). The lobular area of air trapping
(black arrow) in the left lower lobe underwent a postexpiratory
increase in lung attenuation of 40 Hounsfield units (HU). In contrast,
the normal appearing lung immediately adjacent to the area of air
trapping increased in attenuation by 155 HU. The CT scan also revealed
several small pulmonary nodules.
View larger version (105K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1. Top, A: Inspiratory HRCT
reveals mosaic attenuation at the lung bases. A lobular area of
decreased attenuation in the left lower lobe is demarcated (black
arrow). Bottom, B: Expiratory HRCT performed
at approximately the same level as the above image. The lobular
area of decreased attenuation in the left lower lobe remains lucent on
expiration (black arrow). This confirms air trapping. Multiple other
areas of air trapping are also present.
|
|
When the patient presented for diagnostic bronchoscopy, his symptoms
had progressed with worsening shortness of breath, chills, and
cyanosis. The pulse oximetry revealed the saturation to be consistently
below 88%. Transbronchial biopsies were performed of the right lower
lobe after endobronchial exploration revealed no abnormalities. BAL was
performed and was negative for atypical cells or infection. He was
admitted to the hospital for further evaluation and treatment.
Histologic examination of biopsy sections revealed prominent capillary
expansion within the alveolar and peribronchial interstitial tissue by
a cellular infiltrate. The alveolar walls appeared rigid, and the
alveolar spaces were not involved by the process (Fig 2
). The infiltrate was composed of large cells with little cytoplasm,
high nucleus to cytoplasm ratios, and irregular nuclear contours. Many
cells had vesicular nuclei with peripheral chromatin condensation and
one to three nucleoli. Immunohistochemistry studies revealed positive
staining in tumor cells with leukocyte common antigen (Dako; Gloftrup,
Denmark) and L-26 (Dako), which identified the tumor as a lymphoma of
B-cell lineage (Fig 3
). The stains further demonstrated that the tumor cells were confined to
the expanded capillary lumena in both the alveolar septa and in the
tissue adjacent to the bronchioles. The tumor cells were negative for
the T-cell marker UCHL-1 (Dako) and cytokeratin (Kermix; Dako;
Indianapolis, IN).
View larger version (142K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2. Histologic section demonstrating expansion in
alveolar and peribronchial interstitial tissue by lymphoma. The
alveolar spaces are free of involvement by the process. An arteriole
with a patent lumen is present (black arrow) with no identifiable
adjacent bronchiole (hematoxylin-eosin, original magnification
x200).
|
|
View larger version (96K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3. Immunohistochemistry staining of tumor cells
within alveolar capillaries with L-26, demonstrating a strong staining
reaction and highlighting some of the cytologic characteristics of the
tumor (original magnification x400).
|
|
The patient received 6 cycles of systemic combination chemotherapy with
cyclophosphamide, doxorubicin, vincristine, and prednisone without
complications and obtained a complete remission. After treatment,
repeat pulmonary function testing revealed marked improvement with an
FVC of 4.71 L (120% predicted), FEV1 of 2.94 L
(98% predicted), and FEV1/FVC ratio of 65%. The
diffusion capacity increased to 13.82 mL/min/mm Hg (53% predicted).
Total lung capacity remained approximately the same at 9.32 L (150%
predicted), but the residual volume decreased to 4.75 L (207%
predicted). Repeat HRCT performed after treatment revealed interval
resolution of the pulmonary nodules and mosaic perfusion pattern. Since
then, the LDH has decreased to 169 U/L, and the patient has resumed
working, no longer requires supplemental oxygen, and is disease-free at
14 months follow-up.
|
Discussion
|
|---|
IVL is a rare neoplasm that remains confined primarily to the
lumena of small capillaries, venules, and arterioles. This malignancy
was originally believed to be of endothelial origin; however, further
studies revealed the lymphoid, typically B-cell, origin of the
disease.2
3
The reason why these cells stay within the
vasculature and do not involve lymph nodes and organ parenchyma remains
unknown. In the majority of cases, clinical manifestations of IVL have
included cutaneous nodules or plaques, fever, neurologic abnormalities,
including dementia or focal defects, anasarca, and renal
failure.3
Pulmonary vascular involvement with IVL but
without other organ involvement has rarely been reported and is a
difficult antemortem diagnosis.5
6
7
8
9
10
The clinical
presentations are nonspecific and include dyspnea, fever, cough, night
sweats, and the syndrome of inappropriate secretion of antidiuretic
hormone.9
In addition, the serum LDH is commonly elevated.
Pulmonary IVL shares many clinical features with pulmonary tumor
embolism, a syndrome in which malignant cells from a distant tumor such
as breast, lung, and prostate carcinoma embolize to the pulmonary
vasculature. In both diseases, patients frequently experience dyspnea,
tachypnea, and hypoxemia. The malignant cells in pulmonary tumor
embolism, however, induce intravascular thrombosis and intimal
proliferation, which may lead to complete and irreversible obstruction
with resulting pulmonary hypertension and cor pulmonale.12
In contrast, thrombosis and intimal proliferation have been rarely
reported in pulmonary IVL, and there has been only one report of
pulmonary hypertension and cor pulmonale.7
In pulmonary
IVL, there is no lymphadenopathy or localizing mass, and the
radiographic evaluation can be unremarkable5
or show
interstitial infiltrates6
and ground-glass
opacities.10
Pulmonary function testing is
typically remarkable for a decrease in diffusion capacity with
normal,7
10
restrictive,6
or
obstructive5
patterns reported on spirometry. Our case
represents the first case where marked air trapping has been observed
on both plethysmography and high-resolution CT, and the third reported
case where the diagnosis was made by transbronchial
biopsy.5
10
Mosaic perfusion on HRCT may have several etiologies. It is commonly
seen in patients with small airway diseases, which result in focal air
trapping or decreased ventilation of lung parenchyma. Reflex
vasoconstriction results in a poorly ventilated lung becoming poorly
perfused. This is a frequent finding in patients with bronchiolitis
obliterans but can be seen in any disease associated with small airways
obstruction such as cystic fibrosis or bronchiectasis of any cause. Air
trapping is best seen on expiratory HRCT when the abnormality is patchy
in distribution, because normal lung can then be contrasted with
abnormal, lucent lung on the expiratory images. Measuring lung
attenuation increase with expiration may help confirm that the abnormal
lucency represents air trapping.13
Normal lung usually
increases in attenuation by 150 HU or more on expiration; areas of lung
that trap air often show an increase in attenuation of less than 50 HU,
as noted in our patient.
Mosaic perfusion is also associated with pulmonary vascular
obstruction, usually from pulmonary embolism.14
Also,
patchy areas of ground-glass opacity can simulate a mosaic perfusion
pattern. In these cases, postexpiratory HRCT can be very helpful in
differentiating mosaic perfusion related to airways obstruction from
other causes. Expiratory HRCT will accentuate differences in lung
attenuation resulting from airways obstruction; this is not the case
with ground-glass opacity or pulmonary vascular obstruction. The mosaic
perfusion in our patient, therefore, is most consistent with air
trapping, which was confirmed by plethysmography. The vascular
obstruction that IVL causes, however, may have contributed to the
dramatic mosaic perfusion that was observed in our patient.
The etiology of the air trapping in our patient remains unclear.
Histopathology revealed expansion of the peribronchiolar interstitial
tissue, which may compromise small airways by extrinsic compression. In
addition, decreased blood flow to alveoli has been shown to result in
reflex bronchoconstriction, an effect thought to be due to alveolar
hypocapnia.15
The intravascular malignant cells in our
patient could have compromised blood flow enough to cause air trapping
by this mechanism. Local mediators may have also contributed to local
edema or bronchoconstriction.
IVL is potentially curable. Reports of long-term disease-free survival
and presumed cure have been achieved with the use of combination
chemotherapy for intermediate and high-grade lymphomas. Unfortunately,
assessment of therapeutic interventions are difficult to analyze
because of the relatively small number of cases managed antemortem as
well as the lack of randomized studies and adequate long term follow
up. DiGiuseppe et al 4
identified 35 cases treated
with different combination chemotherapy regimens and noted a 54%
complete response rate. Five patients had no evidence of disease at a
median of 48 months and were considered to be cured. Demirer et al5
reviewed 23 patients who received therapy for IVL, and 6
of 11 patients (55%) receiving cyclophosphamide, doxorubicin,
vincristine, and prednisone obtained a complete response.
In summary, our case demonstrates that IVL should be considered in the
differential diagnosis when mosaic perfusion seen on HRCT is associated
with air trapping on plethysmography. Other common clinical
features include fever, weight loss, night sweats, and high elevations
in serum LDH. This case also demonstrates the potential diagnostic
utility of transbronchial biopsy in making the diagnosis early and
relatively noninvasively. As has been reported, a standard lymphoma
treatment regimen may result in a dramatic clinical response as
demonstrated with our patient.
|
Footnotes
|
|---|
The views expressed in this article are those of the authors and do not
reflect the official policy of the Department of Defense or other
Departments of the U.S. Government.
Abbreviations: HRCT = high-resolution CT;
HU = Hounsfield units; IVL = intravascular lymphomatosis;
LDH = lactate dehy-drogenase
Received for publication April 24, 1998.
Accepted for publication August 26, 1998.
|
References
|
|---|
-
Pfleger, L, Tappeiner, J (1959) Zur Kenntnis der Systemisdien Endotheliomatose der Cutanen Blutgefasse. Hautarzt 10,359-363[Medline]
-
Sheibani, K, Battifora, H, Winberg, C, et al (1986) Further evidence that "malignant angioendotheliomatosis" is an angiotropic large-cell lymphoma. N Engl J Med 314,943-948[Abstract]
-
Wick, MR, Mills, SE, Scheithauer, BW, et al (1986) Reassessment of malignant "angioendotheliomatosis: " evidence in favor of its reclassification as "intravascular lymphomatosis." Am J Surg Pathol 10,112-123[ISI][Medline]
-
DiGiuseppe, JA, Nelson, WG, Seifter, EJ, et al (1994) Intravascular lymphomatosis: a clinicopathologic study of 10 cases and assessment of response to chemotherapy. J Clin Oncol 12,2573-2579[Abstract/Free Full Text]
-
Demirer, T, Dail, DH, Aboulafia, DM (1994) Four varied cases of intravascular lymphomatosis and a literature review. Cancer 73,1738-1745[CrossRef][ISI][Medline]
-
Tan, TB, Spaander, PJ, Blaisse, M, et al (1988) Angiotropic large cell lymphoma presenting as interstitial lung disease. Thorax 43,578-579[Abstract]
-
Snyder, LS, Harmon, KR, Estensen, RD (1989) Intravascular lymphomatosis (malignant angioendotheliomatosis) presenting as pulmonary hypertension. Chest 96,1199-1200[Abstract/Free Full Text]
-
Yousem, SA, Colby, TV (1990) Intravascular lymphomatosis presenting in the lung. Cancer 65,349-353[CrossRef][ISI][Medline]
-
Pellicone, JT, Goldstein, MD (1990) Pulmonary malignant angioendotheliomatosis: presentation with fever and syndrome of inappropriate antidiuretic hormone. Chest 98,1292-1294[Abstract/Free Full Text]
-
Takamura, K, Nasuhara, Y, Mishina, T, et al (1997) Intravascular lymphomatosis diagnosed by transbronchial lung biopsy. Eur Respir J 10,955-957[Abstract]
-
Webb, WR (1994) HRCT of obstructive lung disease. Radiol Clin North Am 32,745-757[ISI][Medline]
-
Bassiri, AG, Haghighi, B, Doyle, RL, et al (1997) Pulmonary tumor embolism. Am J Respir Crit Care Med 155,2089-2095[ISI][Medline]
-
Webb, WR, Miller, NL, Naidich, DP (1996) High-resolution CT of the lung. ,90-94 Lippincott-Raven New York, NY.
-
King, MA, Bergin, CJ, Yeung, DWC, et al (1994) Chronic pulmonary thromboembolism: detection of regional hypoperfusion with CT. Radiology 191,359-363[Abstract/Free Full Text]
-
Severinghaus, JW, Swenson, EW, Finley, TN, et al (1961) Unilateral hypoventilation produced in dogs by occluding one pulmonary artery. J Appl Physiol 16,53-60[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
J. Cadranel, M. Wislez, and M. Antoine
Primary pulmonary lymphoma
Eur. Respir. J.,
September 1, 2002;
20(3):
750 - 762.
[Abstract]
[Full Text]
[PDF]
|
|
|
TOP
Abstract
Introduction
