Leukemia Research 24 (1999) 175 – 178

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Case of the month

Pulmonary leukostasis mimicking pulmonary embolism
David A. Kaminsky *, Craig G. Hurwitz, Jennifer I. Olmstead
Pulmonary Disease and Critical Care Medicine, Fletcher Allen Health Care, Uni6ersity of Vermont College of Medicine, Gi6en C-317,
Burlington, VT 05405, USA

Received 16 June 1999; accepted 21 July 1999

Abstract

We report a case of a 32-year-old woman who presented with shortness of breath and pleuritic chest pain, and mismatched
perfusion defects on a ventilation–perfusion scan suspicious for pulmonary embolism. However, subsequent data revealed the
diagnosis of acute myelogenous leukemia with hyperleukocytosis and associated pulmonary leukostasis. Unfortunately, the patient
died despite urgent leukopharesis. Autopsy examination revealed extensive infiltration of leukemic cells in all major organs with
no evidence of pulmonary embolism. This case highlights the clinical, radiographic and histologic features of pulmonary
leukostasis, and reminds the clinician that not all ventilation – perfusion mismatching is due to thromboembolic disease. © 2000
Elsevier Science Ltd. All rights reserved.

Keywords: Leukostasis; Acute myelogenous leukemia; Pulmonary embolus

1. Introduction 2. Case report

One of the most devastating complications of acute
leukemia is the development of hyperleukocytosis and
the leukostasis syndrome. This syndrome involves the
occlusion of small blood vessels primarily in the lungs
and brain, but all major organs may be involved. When
the pulmonary microvasculature is involved, severe res-
piratory distress and hypoxemia may occur. Such
symptoms may be associated with a variety of diagno-
sis’, but when a chest X-ray is relatively clear, the
diagnosis of pulmonary embolism (PE) is commonly
entertained. We present the case of a young woman
who complained of such symptoms and was presump-
tively diagnosed as having PE, whereas these symptoms
were actually her initial manifestation of acute leukemia
with pulmonary leukostasis.
Abbre6iations: ABG, arterial blood gas; AML, acute myelogenous
leukemia; DVT, deep vein thrombosis; H&E, Hematoxylin and
Eosin; PE, pulmonary embolism; V/Q, ventilation/perfusion; WBC,
white blood cell.
* Corresponding author. Tel.: + 1-802-8476973; fax: +1-802-
8476961.
E-mail address: dkaminsk@zoo.uvm.edu (D.A. Kaminsky)
A 32-year-old woman presented with progressive
shortness of breath and pleuritic chest pain. She had
been well until 7 days prior to admission when she
developed a dry cough, shortness or breath, low grade
fevers and general malaise. On the day of admission,
the patient presented with worsened shortness of
breath, sharp, pleuritic chest pain and lower extremity
edema. A chest radiograph was interpreted as normal,
but an arterial blood gas (ABG) on room air showed a
paO2 of 39 mmHg. A presumptive diagnosis of PE was
made, intravenous heparin was started and the patient
was transferred to our institution.
On physical examination, the patient was diaphoretic
and in significant respiratory distress. The temperature
was 38.5°C, the blood pressure 140/85, the pulse 130
beats per min and the respirations 30 per min. Auscul-
tation of the lungs revealed crackles at the left base,
and there was symmetric edema in both lower
extremities.
Arterial blood gases on room air were pH 7.49, pCO2
34 mmHg, pO2 42 mmHg. An electrocardiogram
showed sinus tachycardia with a right-sided strain pat-

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176 D.A. Kaminsky et al. / Leukemia Research 24 (2000) 175–178

Fig. 1. Anterior – posterior portable chest radiograph of the patient

lying at 30° upright. The pulmonary vasculature is prominent and
there is a hazy airspace filling process at the left base.

tern. A chest radiograph (Fig. 1) showed small lung Fig. 2. Anterior (top) and posterior (bottom) views of the ventilation
volumes, prominent central pulmonary arteries, and a (left) and perfusion (right) lung scans. Mismatched perfusion defects
hazy airspace filling process at the left base. There was are seen in the right upper lobe.
no evidence of deep vein thrombosis (DVT) by ultra-
sound examination of the lower extremities, but a venti- throughout the vessels and parenchyma of the lungs
lation–perfusion (V/Q) scan (Fig. 2) was read as (Figs. 3 and 4), including the areas of infarction. In
high-intermediate probability for PE, with two mis- addition, there were numerous thrombi in small vessels
matched perfusion defects in the right upper lobe, so without signs of infarction (Fig. 5). These thrombi
heparin was continued. appeared to have been formed recently antemortem,
Subsequent laboratory data revealed a white blood because Trichrome stains did not show the signs of
cell (WBC) count of 305 000 per ml, with 84% blast collagen deposition and organization that would be
forms and 12% promyelocytes, consistent with the expected for more subacute disease. Given the lack of
diagnosis of acute myelogenous leukemia (AML). evidence for lower extremity DVT by ultrasound exam-
The hematocrit value was 31% and the platelet count ination, or clot elsewhere by autopsy examination, the
64 000 per ml, and the patient had coagulation
defects consistent with disseminated intravascular coag-
ulation.
A diagnosis of AML, type M5, with probable
pulmonary leukostasis was made, although con-
comitant PE could not be ruled out, and oxygen,
intravenous fluids, heparin, allopurinol and hydrox-
yurea were administered. Urgent leukapheresis
was performed, with a reduction in the WBC count
by 37% to 190 000 per ml. Unfortunately, the next
day, the patient developed acute right-sided hemiparesis
and cardiac arrest characterized by pulseless elec-
trical activity, and she died despite full resuscitative
efforts.
Autopsy examination showed extensive infiltration
by leukemic cells of all organs, including the heart,
lungs, liver, spleen, kidneys, lymph nodes, bone marrow
and brain. Pulmonary infarction with hemorrhage was
noted in both lower lobes, with an associated arterial Fig. 3. Light micrograph of the lung at autopsy, showing extensive
filling of a pulmonary artery with leukemic cells, as well as leukemic
thrombus in a minor arterial branch of the right lower
infiltration of adjacent alveolar capillaries. Hematoxylin and Eosin
lobe. Extensive leukemic infiltration was noted (H&E), 10 ×.
 D.A. Kaminsky et al. / Leukemia Research 24 (2000) 175–178
Fig. 4. Light micrograph at higher power of the lung in Fig. 3,
showing leukemic infiltration of the alveolar capillaries. H&E, 20 × .
thrombi in the lungs were felt most likely to have
formed in situ, with an embolic origin being less likely.
3. Discussion
This patient illustrates the severe consequences of the
pulmonary leukostasis syndrome associated with AML,
including the mismatching of ventilation and perfusion
on nuclear lung scanning that may mimic pulmonary
thromboembolic disease. Leukostasis typically occurs
with a WBC count of greater than 100 000 per ml, [1].
As the WBC increases, and the relative percentage of
WBCs approaches 10 – 15%, the total blood viscosity
increases due to the decreased deformability of the
abnormal leukocytes [2]. The result is cell clumping and
stasis in the microvasculature, leading to organ dys-
function and related symptoms.
The blocking of the pulmonary microvasculature re-
sults in pulmonary leukostasis syndrome, characterized
Fig. 5. Light micrograph of the lung at autopsy showing a recent
thrombus in a pulmonary artery. H&E, 2.5 × .
177
by hypoxemia, variable radiographic infiltrates and res-
piratory distress [3]. Pulmonary leukostasis with sludg-
ing of WBCs in the capillary bed can cause V/Q
mismatching, disrupt capillary endothelial integrity and
lead to diffuse capillary leak [3]. In addition, the large
numbers of WBCs consume oxygen and may result in a
direct lowering of the pO2 in samples of blood obtained
for analysis [4]. The radiographic appearance of pul-
monary leukostasis is variable, ranging from normal,
thought to be due to microvascular leukostasis only, to
diffuse alveolar consolidation, most likely related to
pulmonary edema from leaky vessels or concomitant
cardiac dysfunction [5].
The presence of pulmonary leukostasis in AML has
been associated with a worse overall prognosis [6]. In
one study, only 27% of patients with AML and pul-
monary leukostasis achieved remission compared with
64% of those with AML without pulmonary leukostasis
[6]. In this study, the median survival of patients with
AML and pulmonary leukostasis was only 0.2 months,
compared with 10.8 months in patients with no
leukostasis.
Aggressive treatment with leukapheresis is essential
in achieving a favorable outcome [6]. In the study by
Lester and colleagues, remission was more likely in
patients who had a greater than 30% reduction in the
initial WBC count [6]. In addition to instituting defini-
tive antileukemic treatment, other principles of therapy
include avoiding intravascular volume depletion by ex-
cessive diuresis [7] and unnecessary blood transfusions
[8], both of which can increase blood viscosity. Leuka-
pheresis should ideally be performed before starting
chemotherapy to minimize the tumor burden and there-
fore the adverse metabolic effects of tumor lysis [9].
This case involved respiratory distress from pul-
monary leukostasis associated with AML. The severe
hypoxemia noted on ABG analysis was likely a conse-
quence of both true hypoxia from the microvascular
lung infiltration, as well as the local effects of increased
oxygen consumption in the blood sample. In the setting
of an apparently normal chest radiograph and leg
edema, the diagnosis of PE was appropriately enter-
tained. This diagnosis was further supported by the
findings on V/Q scan, but perfusion defects would be
expected in both pulmonary leukostasis and PE. In-
deed, many processes that involve the pulmonary vas-
culature have been described as causing V/Q
mismatches on nuclear lung scanning [10,11]. Such
processes, like vasculitis [12], lymphangitic carcinoma
[13], or embolism of fat [14] or foreign matter [15],
primarily involve the pulmonary vasculature and there-
fore result in perfusion defects without concomitant
ventilatory abnormalities. Likewise, bronchogenic car-
cinoma [16], or other processes that involve hilar or
mediastinal structures, may selectively impinge on pul-
monary vessels but not on airways, and therefore also
178 D.A. Kaminsky et al. / Leukemia Research 24 (2000) 175–178
result in a similar pattern of mismatched defects. Usu-
ally, the clinical scenario, together with concomitant
chest imaging by plain radiograph or computed tomog-
raphy, and other more subtle hints on perfusion imag-
ing [11], help to differentiate these possibilities. A
radiographic clue of a process mimicking PE is the
finding of a solitary lung or lobar perfusion defect that
persists over 1 week, since most PEs present as bilat-
eral, multiple mismatched perfusion defects that change
over time [11]. Of course, if the diagnosis of PE remains
clinically important to determine, pulmonary angiogra-
phy should be performed.
Autopsy examination in this case clearly demon-
strated the striking pathology of pulmonary leukostasis.
The pulmonary vasculature, and in particular, the cap-
illary bed, was extensively infiltrated with tumor cells.
In fact, very few red blood cells were seen. Knowing the
rheologic properties of such blood as mentioned earlier,
it is amazing that any gas exchange took place at all.
While the lung histology did demonstrate some areas of
infarction, these appeared to be due to either recent in
situ thrombosis or infarction related to local leukemic
infiltration, not due to embolic disease. Thus, there was
no clear evidence of PE in this case.
Acknowledgements
DA Kaminsky provided the concept, design, con-
tributed to the analysis and interpretation, drafted the
article, provided critical revision and gave final ap-
proval. In addition, he provided patient material, tech-
nical support and helped to assemble the data. CG
Hurwitz helped with the drafting of the paper, provided
study materials, technical support and helped to assem-
ble the data and gave final approval. JI Olmstead
assisted with data analysis, gave final approval, pro-
vided study materials and technical support.
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