A case of leukemic pleural infiltration in atypical chronic myeloid leukemia.
ABSTRACT Pleural effusion in chronic myeloid leukemia (CML) is poorly understood and rarely reported in the literature. When the pleural effusion is caused by leukemic pleural infiltration, the differential white blood cell count of the effusion is identical to that of the peripheral blood, and the fluid cytology reveals leukemic blasts. We report here a case of bilateral pleural involvement of atypical CML in an 83-yr old male diagnosed with pancreatic cancer with abdominal wall metastasis and incidental peripheral leukocytosis. Based on bone marrow examination, chromosome analysis and polymerase chain reaction he was diagnosed with Philadelphia chromosome negative, BCR/ABL gene rearrangement negative CML. Following 3 months of treatment with gemcitabine for pancreatic cancer, he developed bilateral pleural effusions. All stages of granulocytes and a few blasts were present in both the pleural fluid and a peripheral blood smear. After treatment with hydroxyurea and pleurodesis, the pleural effusion resolved.
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ABSTRACT: Pulmonary manifestations have been well described in leukemia, but pleural disease is less common. This review highlights pleural effusions in acute and chronic leukemia and myelodysplastic syndrome (MDS) based on the evidence to date. Diagnostic workup and recommendations for the management of these effusions are also outlined. Pleural effusions in patients with leukemia are most often due to infection and to a lesser extent leukemic infiltration of the pleura. The prognostic implications of these effusions are unclear, but survival is most likely determined by the underlying malignancy and its response to treatment. New therapies have changed survival in these patients, and some of these treatments, such as tyrosine kinase inhibitors, have emerged as important causes for these effusions. Pleural interventions may be accomplished with few complications. Pleural effusions may occur with acute and chronic leukemia and MDS. Infection remains the most common cause. Malignant pleural effusions tend to occur in advanced disease in chronic leukemia, but they can be seen at any time with acute leukemia and MDS. With standard precautions, pleural procedures may be performed safely in this population. In cases of unclear cause, pleural and bone marrow biopsy should be considered.Current opinion in pulmonary medicine 05/2014; · 2.96 Impact Factor
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ABSTRACT: Pleural effusions are a common problem in patients with malignancies. It can present as an isolated entity or be associated with parenchymal lung abnormalities. Patients with hematological malignancies (HM) can present with pleural effusion at diagnosis or may develop it during the course of their underlying disease. Regarding etiology, various causes can stimulate the accumulation of pleural fluid: the disease itself, drug toxicity, radiotherapy, underlying infections, secondary malignancies, autoimmunity, extramedullary hematopoiesis and other complications. Thoracentesis is a simple, safe and well-tolerated procedure in patients with HM.
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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.Journal of Cytology 04/2012; 29(2):152-4. · 0.31 Impact Factor
Atypical chronic myeloid leukemia (CML) is negative for
both the Philadelphia chromosome and BCR/ABL gene rear-
rangement (1). During the course of CML, 37% of patients
develop extramedullary disease in sites such as the lymph
nodes, spleen, or meninges (2), but, pleural effusion due to
leukemic infiltration in this disease is rare. In this paper, we
describe a patient who developed pleural effusion during treat-
ment for atypical CML and pancreatic cancer. The pleural
effusions were cleared after treatment with hydroxyurea and
An 83-yr-old male patient with leukocytosis was admitted
to our hospital on September, 2004. His medical history in-
cluded an early gastric cancer and distal gastrectomy in 1989,
and a right lobectomy for non small cell lung cancer in May
2004. One month prior to the admission, he was diagnosed
as having pancreatic tail cancer with abdominal wall metas-
tasis, which had not been treated surgically or with chemo-
On physical examination, the patient’s liver and spleen were
not palpable. A tender and firm mass, measuring 1×2 cm,
was noted on the periumbilical abdominal wall. Hematologic
findings were Hb 10.6 g/dL, WBC 71×109/L (neutrophil
58%, lymphocyte 7%, monocyte 13%, eosinophil 3%, pro-
myelocyte 2%, myelocyte 10%, metamyelocyte 4%, blast 1%,
normoblast 1/100 WBC), and platelet 192×109/L. Patho-
logic examination showed that his palpable abdominal wall
mass was a metastatic adenocarcinoma that differed from the
previous non small cell lung cancer. Immunohistochemically,
the tumor cells were positive for cytokeratin 7 (CK7) and
negative for thyroid transcription factor 1 (TTF-1) and cyto-
keratin20 (CK20), whereas his non small cell lung cancer cells
had been positive for TTF-1 and CK7 and negative for CK20.
Bone marrow examination showed hypercellular marrow (cel-
lularity 90%) containing cells at all stages of granulocytic
hyperplasia and 0.6% blasts. There were some hypogranular
myelocytes, indicating dysgranulopoiesis (Fig. 1). Polymerase
chain reaction for BCR/ABL fusion gene was negative. The
leukocyte alkaline phosphatase (LAP) activity score was 13
(reference range 30-130). Computed tomography of the ab-
domen showed a solid mass in the tail of the pancreas with
attachment to the spleen and invasion of the spleen and splenic
artery by the mass, leading to splenic infarction (Fig. 2). Based
on these results, he was diagnosed with atypical CML. He
was treated with gefitinib 250 mg/day for metastatic pancre-
atic cancer and hydroxyurea 1,500 mg/day plus allopurinol
for atypical CML. Treatment with hydroxyurea was interrupt-
Hyun Woo Kim, Sung Sook Lee,
Min-Hee Ryu, Jae Lyun Lee,
Heung Moon Chang, Tae Won Kim,
Hyun-Sook Chi*, Woo Kun Kim,
Jung Shin Lee, Yoon-Koo Kang
Departments of Internal Medicine, Laboratory
Medicine*, University of Ulsan College of Medicine,
Address for correspondence
Yoon-Koo Kang, M.D.
Department of Internal Medicine, University of Ulsan
College of Medicine, 388-1 Poongnap-dong,
Songpa-gu, Seoul 138-736, Korea
Tel : +82.2-3010-3210, Fax : +82.2-3010-6961
E-mail : firstname.lastname@example.org
J Korean Med Sci 2006; 21: 936-9
Copyright � The Korean Academy
of Medical Sciences
A Case of Leukemic Pleural Infiltration in Atypical Chronic Myeloid
Pleural effusion in chronic myeloid leukemia (CML) is poorly understood and rarely
reported in the literature. When the pleural effusion is caused by leukemic pleural
infiltration, the differential white blood cell count of the effusion is identical to that of
the peripheral blood, and the fluid cytology reveals leukemic blasts. We report here
a case of bilateral pleural involvement of atypical CML in an 83-yr old male diagnosed
with pancreatic cancer with abdominal wall metastasis and incidental peripheral
leukocytosis. Based on bone marrow examination, chromosome analysis and poly-
merase chain reaction he was diagnosed with Philadelphia chromosome negative,
BCR/ABL gene rearrangement negative CML. Following 3 months of treatment with
gemcitabine for pancreatic cancer, he developed bilateral pleural effusions. All stages
of granulocytes and a few blasts were present in both the pleural fluid and a peri-
pheral blood smear. After treatment with hydroxyurea and pleurodesis, the pleural
Key Words : Pleural Effusion; Atypical Chronic Myeloid Leukemia; Leukemia, Myeloid, Chronic
Received : 27 June 2005
Accepted : 17 August 2005
Pleural Infiltration in Atypical Chronic Myeloid Leukemia
ed intermittently when WBC count of the peripheral blood
decreased to 10×109/L or less. Beginning in November 2004,
he was treated with gemcitabine for pancreatic cancer, inter-
rupted periodically because of infectious diarrhea, acute renal
failure due to use of aminoglycoside antibiotics and skin rash.
At that time, treatment with hydroxyurea was stopped due
After 3 months of treatment with gemcitabine, the patient
experienced progressive dyspnea and fatigue, as well as being
tachypneic (30/min) and pale. Pulmonary examination revealed
decreased bilateral breathing sounds and chest radiograph
showed bilateral pleural effusion (Fig. 3). Right thoracente-
sis was performed and 1,400 mL of serous fluid was aspirat-
ed. Analysis of the pleural fluid showed glucose 109 mg/dL,
protein 2.2 g/dL (serum protein 4.6 g/dL), albumin 1.1 g/dL
(serum albumin 2.0 g/dL), LDH 386 IU/L (serum LDH 1,064
IU/L, reference range 120-250 IU/L), adenosine deaminase
23U/L, hematocrit 6.0%, WBC count 2,390 / L (neutrophil
Fig. 1. (A) Smear of marrow aspirate showing increased numbers of granulocytes at all stages of development and blasts (Wright-Giemsa
stain, ×400). (B) Smear of marrow aspirate showing hypogranular myelocytes (arrow) (Wright-Giemsa stain, ×1,000).
Fig. 2. Computed tomography of the abdomen demonstrating a
solid mass in the tail of the pancreas with attachment to the spleen.
Fig. 3. Radiograph of the chest revealing bilateral pleural effusion.
H.W. Kim, S.S. Lee, M.-H. Ryu, et al.
51%, lymphocyte 19%, histiocyte 9%, band form 6%, pro-
myelocyte 3%, myelocyte 5%, metamyelocyte 5%, normo-
blast 3/100 WBC, blast 2%) (Fig. 4). Hematologic findings
of the peripheral blood were Hb 8.7 g/dL, WBC 150×109/L
(neutrophil 62%, lymphocyte 7%, monocyte 5%, promye-
locyte 2%, myelocyte 18%, metamyelocyte 5%, blast 0%,
normoblast 1/100 WBC), platelet 109×109/L. The ratio of
erythrocytes to nucleated cells in the effusion was 8 as com-
pared to a ratio of 18 in the blood, suggesting that the nucle-
ated cells in the effusion were not solely due to bleeding into
the pleural cavity. The pleural fluid was negative for Gram
stain and acid fast bacilli. The patient was diagnosed with
CML complicated with pleural effusion. Bilateral chest drainage
catheters were inserted to control the pleural effusion. The
patient was retreated with hydroxyurea and allopurinol, and
the amount of pleural fluid decreased in accord with the de-
crease in the WBC count of peripheral blood. Due to loculat-
ed pleural effusion, however, the effusion did not completely
resolve. At this point, a right chest tube was substituted for
the right chest drainage catheter. Pleurodesis was performed
for the right pleural effusion, thus relieving dyspnea of the
patient. Two months after the appearance of the pleural invol-
vement, the patient died due to hypercarbic respiratory fail-
ure. Until that time, however, no peripheral blood blast cri-
sis was detected.
Development of extramedullary disease in the pleura of
patients with CML is frequently accompanied by increased
blasts in the pleural fluid. Analysis of pleural fluid, however,
does not always show excess blasts, and in some cases, all stages
of granulocytes and a few blasts are found in the pleural fluid
or ascites (9, 11). Categorization of the cytomorphologic fea-
tures of extramedullary diseases in 18 patients with CML
showed that extramedullary disease could be sorted into 3
types, depending on the proportion of blasts to more mature
differentiated granulocytic cells (6). These 3 categories were
blastic, showing a predominance of blasts (5 patients, 28%);
immature, showing a predominance of blasts and other non-
blastic myeloid precursors (8 patients, 54%); and mature,
with a full spectrum of granulocytic maturation from blasts
to granulocytes (5 patients, 28%).
The patient described here had serous pleural effusion after
3 months of treatment with hydroxyurea and gemcitabine.
Because he had multiple malignancies and the pleural fluid
was an exudate, we hypothesized that the pleural effusion of
the patient was caused by his malignancies. Pleural fluid cyto-
logy, however, showed no evidence of gastric, lung or pancre-
atic cancer cells but revealed premature and mature leuko-
cytes, and variable numbers of blasts. We therefore regarded
the pleural effusion of the patient as related to CML.
There are several possible mechanisms of exudative pleural
effusion in CML patients. The first mechanism is leukemic
infiltration into the pleura, which usually occurs at the time
of or just prior to bone marrow evolution to blast crisis phase
(2, 3). The most common sites are the lymph nodes, bone and
nervous system, while infiltration of the brain, testis, skin,
breast, soft tissues, synovia, gastrointestinal tract, ovaries, kid-
neys and pleura occur less frequently (4). Involvement of the
pleura has been rarely documented, and isolated pleural blast
crisis in the absence of medullary transformation is extremely
rare (2). In these cases, pleural fluid analysis revealed vari-
able stages of granulocytes and leukemic blasts.
The second mechanism is pleural reaction secondary to
bleeding into the pleural cavities that may cause pleural effu-
sion in the patient with CML (5). Predisposing factor such
as leukostasis and platelet dysfunction may have a role in hem-
orrhagic effusion. Thus, the cytologic findings in the effusion
are due to leukemic cell contamination and pleural reaction
as a result of bleeding into the pleural cavity. If this is true,
the ratio of red blood cells to nucleated cells in the blood and
effusion should be similar. In our patient, however, the ratio
of red blood cells to nucleated cells was higher in the blood
than in the pleural effusion, and thus it is more likely that
the large numbers of nucleated cells in the pleural fluid orig-
inated from the pleural cavities.
A third possible mechanism underlying effusion is pleural
extramedullary hematopoiesis. It can present as a discrete mass
in almost any organ, including the liver, spleen, breasts, lymph
nodes, kidneys, thyroid, pancreas, endometrium, and medi-
astinum, or in the serous effusion. But, unlike pleural leuke-
mic infiltration, extramedullary hematopoiesis includes hema-
Fig. 4. Smear of pleural effusion sediment showing several early
granulocytes with morphologic features similar to the cells in the
bone marrow (Wright-Giemsa stain, ×1,000).
Pleural Infiltration in Atypical Chronic Myeloid Leukemia
topoietic cells of the erythroid, myeloid, and megakaryocytic
cells, although one lineage can predominate (6). A fourth
mechanism causing effusion is nonmalignant causes, such as
infection. Therefore, the possibility of infectious process must
be excluded and the presence of necrotic debris and/or the
positive identification of microorganisms by special stains
may suggest an infectious process.
Based on a review of the literature and clinical findings,
leukemic infiltration into pleura was suggested as the cause
of pleural effusion in our patient.
Generally the median time from diagnosis of extramedullary
blast crisis to marrow blast crisis is 4 months, and the medi-
an survival after development of extramedullary transforma-
tion is 5 months (4). Extramedullary disease in CML is con-
sidered an indicator of poor prognosis, which should lead to
a change in therapy and to the institution of treatments usu-
ally reserved for blast crisis (4). Unfortunately, however, there
is no effective standard therapy for pleural effusion in CML.
To the best of our knowledge, there have been only 8 case
reports of isolated pleural infiltration of CML (2-4, 7-10). One
patient responded to thoracentesis and treatment with hydro-
xyurea without recurrence (9), and another patient responded
to systemic chemotherapy with idarubicin and Ara-C (10).
In 5 patients, in which pleural blast antedated hematologi-
cal transformation, intrapleural infusion of chemotherapeu-
tic agents (methotrexate, cytosine arabionside, prednisone)
and systemic chemotherapy were ineffective, and all 5 patients
died within 2 months (3, 4, 7, 8). In the remaining patient,
the type of treatment was not reported (2).
In conclusion, patients with CML should be considered at
risk for development of extramedullary manifestations of blast
crisis while the bone marrow remains in the chronic phase.
Extramedullary blast crisis of CML can occur at any time and
anywhere circulating stem cells are found. In CML patient
with pleural effusions, bleeding into pleural cavity and ext-
ramedullary hematopoiesis should first be considered. If these
causes are ruled out, the presence of leukemic cells in the effu-
sion may denote leukemic involvement of pleura. Pleural infil-
tration of CML adversely affects prognosis.
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