Pulmonary Leukostasis Mimicking Pulmonary Embolism: Case of The Month

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Leukemia Research 24 (1999) 175 – 178

www.elsevier.com/locate/leukres

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

0145-2126/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S 0 1 4 5 - 2 1 2 6 ( 9 9 ) 0 0 1 6 2 - 9
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) 175–178 177

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
Fig. 4. Light micrograph at higher power of the lung in Fig. 3, one study, only 27% of patients with AML and pul-
showing leukemic infiltration of the alveolar capillaries. H&E, 20 × . monary leukostasis achieved remission compared with
64% of those with AML without pulmonary leukostasis
thrombi in the lungs were felt most likely to have [6]. In this study, the median survival of patients with
formed in situ, with an embolic origin being less likely. AML and pulmonary leukostasis was only 0.2 months,
compared with 10.8 months in patients with no
leukostasis.
3. Discussion Aggressive treatment with leukapheresis is essential
in achieving a favorable outcome [6]. In the study by
This patient illustrates the severe consequences of the Lester and colleagues, remission was more likely in
pulmonary leukostasis syndrome associated with AML, patients who had a greater than 30% reduction in the
including the mismatching of ventilation and perfusion initial WBC count [6]. In addition to instituting defini-
on nuclear lung scanning that may mimic pulmonary tive antileukemic treatment, other principles of therapy
thromboembolic disease. Leukostasis typically occurs include avoiding intravascular volume depletion by ex-
with a WBC count of greater than 100 000 per ml, [1]. cessive diuresis [7] and unnecessary blood transfusions
As the WBC increases, and the relative percentage of [8], both of which can increase blood viscosity. Leuka-
WBCs approaches 10 – 15%, the total blood viscosity pheresis should ideally be performed before starting
increases due to the decreased deformability of the chemotherapy to minimize the tumor burden and there-
abnormal leukocytes [2]. The result is cell clumping and fore the adverse metabolic effects of tumor lysis [9].
stasis in the microvasculature, leading to organ dys- This case involved respiratory distress from pul-
function and related symptoms. monary leukostasis associated with AML. The severe
The blocking of the pulmonary microvasculature re- hypoxemia noted on ABG analysis was likely a conse-
sults in pulmonary leukostasis syndrome, characterized 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
Fig. 5. Light micrograph of the lung at autopsy showing a recent mediastinal structures, may selectively impinge on pul-
thrombus in a pulmonary artery. H&E, 2.5 × . 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- References


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