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201]

Case Report

Pleural effusion as the initial manifestation of chronic myeloid

leukemia: Report of a case with clinical and cytologic
correlation
ABSTRACT
Pleural effusion in patients with chronic myeloid leukemia (CML) is very rare and poorly understood. We report here a
26-year-old male patient having CML and presenting with pleural effusion as the first clinical sign. The possible mechanism
of pleural effusion in CML, the cytological interpretive problem and the clinical significance of finding immature leucocytes
in pleural fluid are also briefly discussed.

Key words: Chronic myeloid leukemia; cytology; pleural effusion.

Introduction prolonged medical illness or significant drug therapy.

Pleural effusion in patients with chronic myeloid leukemia
(CML) is a rare occurrence and poorly understood.[1] Still rare
is pleural effusion as an initial manifestation of CML.[2] The
possible mechanisms of exudative pleural effusion in CML
patients include leukemic infiltration into the pleura, extra-
medullary hematopoiesis, non malignant causes and drugs
etc.[3] Below, we report a rare case of CML patient presenting
with pleural effusion as the first clinical sign.
Case Report
A 26-year-old male presented with chief complaints of
breathlessness on exertion, for two weeks, and left side chest
pain for five days. He denied any history of cough, fever,
hemoptysis or bleeding in any form. There was no history of
On examination, patient was afebrile, with stable vital
parameters. There was slight pallor, but no lymphadenopathy,
clubbing, jaundice, pedal edema or evidence of mucocutaneous
bleeds. Respiratory system examination revealed dull note
with decreased intensity of breath sounds at left infra axillary
and infrascapular region. The liver was slightly enlarged,
but spleen was not palpable. The cardiovascular and central
nervous systems were within normal limits. The clinical
impression was anemia with left sided pleural effusion.
Skiagram chest revealed moderate pleural effusion on left
side. About 1.2litres of straw colored fluid was aspirated
under local anesthesia from left pleural space and sent for
cytological analysis. The pleural fluid protein was 4.1g/dl,
glucose 92mg/dl and ADA 10 U/L.

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The straw colored pleural fluid was routinely processed
Quick Response Code
Website: by cyto-centrifugation. The smear revealed numerous
www.jcytol.org myelocytes and neutrophils, with occasional smudge cells
against hemorrhagic background [Figure 1].
DOI:
10.4103/0970-9371.97165 A possibility of leukemia was mentioned in the cytology report,
and a hematologic workup was advised to rule out CML.

Paras Nuwal, Ramakant Dixit1, Prateek Dargar, Jacob George1

Departments of Pathology and 1Respiratory Medicine, J. L. N. Medical College, Ajmer, India

Address for correspondence: Dr. Ramakant Dixit, Consultant Pulmonologist, A-60, Chandravardai Nagar, Ajmer-305 001, Rajasthan, India.
E-mail: dr.ramakantdixit@gmail.com

152 Journal of Cytology / April 2012 / Volume 29 / Issue 2

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Nuwal, et al.: CML presenting as pleural effusion
Figure 1: Microphotograph of pleural fluid cytology showing numerous
myelocytes, neutrophils and smudge cells against hemorrhagic background
(H and E, ×200)
The hemoglobin was 8.5gm% with total leucocyte count
1.15 lacs/mm3. The peripheral blood smear examination
revealed normocytic normochronic anemia with occasional
normoblast. The differential count comprised of myeloblasts
2%, promyelocytes 3%, myelocytes 37%, metamyelocytes
10%, band cells 5% neutrophils 40%, eosinophils 2% and
basophils 1%. The platelets were abundant and normal
in morphology. The peripheral blood smear picture was
suggestive of CML.
Investigations revealed nothing abnormal in urine and blood
biochemistry. The electrocardiogram (ECG) was normal, and
ultrasound revealed mild enlargement of liver and spleen.
Pleural fluid examination did not reveal any pathogenic
organism or acid-fast bacilli and culture was sterile. The
mantoux test was negative and sera was nonreactive for HIV. A
final diagnosis of CML with pleural infiltration was made, and
the patient was referred to oncology department for further
management. Following treatment of CML, there was gradual
decline in pleural effusion that completely disappeared after
three months.
Discussion
During the course of CML, about 37% of patients develop
extra-medullary disease in sites such as lymph nodes,
spleen or meninges, but pleural effusion due to leukemic
infiltration in this disease is rare.[4] Analysis of pleural fluid
may show increased blasts or in some cases, all stages
of granulocytes and a few blasts.[5] In our case, patient
presented with exudative pleural effusion with increased
number of granulocytes at all stages of development. The
cytopathologist was not aware of the clinical findings and for
treating pulmonologist also, there was no clinical finding to
Journal of Cytology / April 2012 / Volume 29 / Issue 2
suggest a hematolymphoid neoplasm. It was the pleural fluid
cytology that raised the possibility of CML and was further
confirmed by peripheral blood smear. Such a presenting
manifestation of CML as pleural effusion is very rare.
Several possible mechanisms of pleural effusion in patients
with CML have been considered. These includes –
(a) Leukemic infiltration into the pleura that usually occurs
at the time of or just prior to bone marrow evolution
to blast crisis phase.[4] In these cases, the pleural fluid
contains a greater proportion of blast cells. Leucocyte
alkaline phosphatase (LAP) activity, known to be low in
CML granulocytes of peripheral blood, has been reported
to be normal in the granulocytes of the pleural effusion.
LAP – negative circulating granulocytes of these patients
with CML were incubated with the pleural fluid, and after
40 to 70 hours almost all were intensely LAP positive. This
finding suggests that a low LAP activity score in resting
CML neutrophils is attributable to the absence of the
appropriate stimuli rather than incapacity to synthesize
the enzyme. Additionally, in Philadelphia chromosome
positive cases, the Philadelphia chromosome is detected
in the pleural granulocytic cells by conventional
cytogenetic methods.[6]
(b) Second possible cause of pleural effusion in CML is
extramedullary hemopoiesis, although the pleura
are rarely a site in these patients.[6] Unlike pleural
leukemic infiltration, extramedullary hematopoiesis
includes hematopoietic cells of the erythroid, myeloid
and megakaryocytic cells, although one linkage can
predominate.[7]
(c) Third mechanism of development of pleural effusions
in CML is the possible obstruction of pleural capillaries
or infiltration of interstitial tissue by leukemic cells
during uncontrolled leucocytosis and increased capillary
permeability due to cytokine production.[6] Predisposing
factors such as leucostasis and platelet dysfunction may
have a role in hemorrhagic effusion of CML. Leucostasis
can cause plugging of blood vessels with secondary
hemorrhage. Marked thrombocytosis and abnormal
platelet function in CML may also add to it.[8]
(d) Non malignant causes like infection and hypoproteinemia
have also been postulated as the cause of effusion.
Therefore, this possibility must be excluded by
identification of microorganisms by special stain and/or
presence of necrotic debris.
(e) The last possible cause of pleural effusion in CML is
drug induced. Dasatinib and imatinib are tyrosine kinase
inhibitor with significant anti-leukemic activity in CML
patients. Their use has been associated with pleural
effusion in 15% cases in one study.[9]
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Nuwal, et al.: CML presenting as pleural effusion

Based on review of literature, clinical findings and
investigation reports, the cause for pleural effusion in our
patient was leukemic infiltration into pleural space. Pleural
effusion in CML is generally considered as poor prognostic
indicator. There is no effective standard treatment of
pleural effusion in CML patients and these patients are
managed with thoracocentesis, treatment of underlying
CML by chemotherapeutic agents and pleurodesis.
In conclusion, pleural effusion associated with hematopoetic
or lymphoid malignancies are rare. Apart from CML, there
are also reports of multiple myeloma and Non-Hodgkins
lymphoma being associated with pleural effusion.[10,11] Pleural
effusion being the presenting feature of the same is very rare.
Awareness of this uncommon situation by both physician and
cytopathologist is critical for the diagnosis and management
of such cases. A cautious approach should be adopted in
interpretation of pleural fluid cytology so as to avoid a false
negative report.
2. Yamazaki E, Kanai M, Sakai R, Sakamoto H, Ishigatsubo Y. Chronic
myelomonocytic leukemia with pleural effusion as the first clinical sign.
Rinsho Ketsueki 2005;46:217-9.
3. Kim HW, Lee SS, Ryu MH, Lee JL, Chang HM, Kim TW, et al. A case
of leukemic pleural infiltration in atypical chronic myeloid leukemia.
J Korean Med Sci 2006;21:936-9.
4. Jones TI. Pleural blast crisis in chronic myelogenous leukemia. Am J
Hematol 1993;44:75-6.
5. Mohapatra MK, Das SP, Mohanty NC, Dash PC, Bastia BK.
Haemopericardium with cardiac tamponade and pleural effusion in
chronic myeloid leukemia. Indian Heart J 2000;52:209-11.
6. Alexandrakis MG, Passam FH, Kyriakou DS, Bouros D. Pleural effusion
in hematologic malignancies. Chest 2004;125:1546-55.
7. Suh YK, Shin HJ. Fine-needle aspiration biopsy of granulocytic sarcoma:
a clinicopathologic study of 27 cases. Cancer 2000;90:364-72.
8. Janckila AJ, Yam LT, Li CY. Immunocytochemical diagnosis of acute
leukemia with pleural involvement. Acta Cytol 1985;29:67-72.
9. Bergeron A, Rea D, Levy V, Picard C, Meignin V, Tamburini J, et al. Lung
abnormalities after dasatinib treatment for chronic myeloid leukemia: a
case series. Am J Respir Crit Care Med 2007;176:814-8.
10. Dhingra K, Sachdev R, Singal N, Nigam S, Jain S. Myeloma presenting as
bilateral pleural effusion – A cytological diagnosis. J Cytol 2007;24:101-2.
11. Kushwaha H, Shashikala P, Hiremath S, Basavaraj HG. Cells in pleural
fluid and their value in differential diagnosis. J Cytol 2008;25:138-43.

References How to cite this article: Nuwal P, Dixit R, Dargar P, George J. Pleural
effusion as the initial manifestation of chronic myeloid leukemia: Report
of a case with clinical and cytologic correlation. J Cytol 2012;29:152-4.
1. Bourantas KL, Tsiara S, Panteli A, Milionis C, Christou L. Pleural effusion
in chronic myeloid leukemia. Acta Haematol 1998;99:34-7. Source of Support: Nil, Conflict of Interest: None declared.

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154 Journal of Cytology / April 2012 / Volume 29 / Issue 2