Journal of Cytology
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Year : 2012  |  Volume : 29  |  Issue : 2  |  Page : 152-154
Pleural effusion as the initial manifestation of chronic myeloid leukemia: Report of a case with clinical and cytologic correlation

1 Department of Pathology, J. L. N. Medical College, Ajmer, India
2 Department of Respiratory Medicine, J. L. N. Medical College, Ajmer, India

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Date of Web Publication12-Jun-2012


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.

Keywords: Chronic myeloid leukemia; cytology; pleural effusion

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

How to cite this URL:
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 [serial online] 2012 [cited 2023 Mar 23];29:152-4. Available from:

   Introduction Top

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 Top

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 prolonged medical illness or significant drug therapy.

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.

The straw colored pleural fluid was routinely processed by cyto-centrifugation. The smear revealed numerous myelocytes and neutrophils, with occasional smudge cells against hemorrhagic background [Figure 1].
Figure 1: Microphotograph of pleural fluid cytology showing numerous myelocytes, neutrophils and smudge cells against hemorrhagic background (H and E, ×200)

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A possibility of leukemia was mentioned in the cytology report, and a hematologic workup was advised to rule out CML.

The hemoglobin was 8.5gm% with total leucocyte count 1.15 lacs/mm 3 . 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 Top

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 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 -

  1. 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]
  2. 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]
  3. 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]
  4. 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.
  5. 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]
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.

   References Top

1.Bourantas KL, Tsiara S, Panteli A, Milionis C, Christou L. Pleural effusion in chronic myeloid leukemia. Acta Haematol 1998;99:34-7.  Back to cited text no. 1
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.  Back to cited text no. 2
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.  Back to cited text no. 3
4.Jones TI. Pleural blast crisis in chronic myelogenous leukemia. Am J Hematol 1993;44:75-6.  Back to cited text no. 4
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.  Back to cited text no. 5
6.Alexandrakis MG, Passam FH, Kyriakou DS, Bouros D. Pleural effusion in hematologic malignancies. Chest 2004;125:1546-55.  Back to cited text no. 6
7.Suh YK, Shin HJ. Fine-needle aspiration biopsy of granulocytic sarcoma: a clinicopathologic study of 27 cases. Cancer 2000;90:364-72.  Back to cited text no. 7
8.Janckila AJ, Yam LT, Li CY. Immunocytochemical diagnosis of acute leukemia with pleural involvement. Acta Cytol 1985;29:67-72.  Back to cited text no. 8
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.  Back to cited text no. 9
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.  Back to cited text no. 10
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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.  Back to cited text no. 11
  Medknow Journal  

Correspondence Address:
Ramakant Dixit
Consultant Pulmonologist, A-60, Chandravardai Nagar, Ajmer-305 001, Rajasthan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-9371.97165

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