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(Chest. 2002;121:527-532.)
© 2002 American College of Chest Physicians

Role of Fine-Needle Aspirates of Focal Lung Lesions in Patients With Hematologic Malignancies*

Philip W. Wong, MD; Tihomer Stefanec, MD; Karen Brown, MD and Dorothy A. White, MD, FCCP

* From the Departments of Medicine (Drs. Wong, Stefanec, and White) and Radiology (Dr. Brown), Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University, New York, NY.

Correspondence to: Dorothy A. White, MD, FCCP, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Pulmonary Medicine C-678, New York, NY 10021; e-mail: whited{at}mskcc.org


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Objectives: To evaluate the yield and safety of transthoracic fine-needle aspiration (FNA) in the diagnosis of pulmonary disease in patients with hematologic malignancy.

Design: Retrospective chart review.

Setting: Tertiary-care medical center.

Patients: Sixty-seven patients with a hematologic malignancy or after bone marrow transplantation (BMT) for a hematologic malignancy who underwent a total of 71 FNAs for diagnosis of an unexplained parenchymal lung lesion from January 1, 1991, to June 30, 1999.

Results: The underlying malignancy was lymphoma in 42 patients (63%), leukemia in 8 patients (12%), after allogeneic BMT in 12 patients (18%), after autologous BMT in 3 patients (4%), and other diseases in 2 patients. Radiographs showed focal abnormalities in all cases, and were nodules in 37%, masses in 37%, focal infiltrates in 21%, and cavitary lesions in 5%. The yield of FNA for a finding specific infection or cancer was 56% (40 of 71 FNAs). The FNA with inflammatory changes was clinically sufficient in another 11 patients for a total yield of 72% (51 of 71 FNAs). The yield for lung cancer was 90% (9 of 10 FNAs), for pulmonary lymphoma was 68% (21 of 31 FNAs), and for infection was 67% (10 of 15 FNAs). Complications occurred in 18 of 71 FNAs (25%), with pneumothorax in 14 patients (20%) and chest tube placement required in 4 patients (6%). Bleeding occurred in six patients (8%), including one death in a patient with abnormal hematologic parameters.

Conclusion: Transthoracic FNA in patients with hematologic malignancy and focal lung lesions has an excellent yield for detecting cancer and a yield comparable to bronchoscopy for the diagnosis of infections. It should be considered a useful diagnostic tool in this setting.

Key Words: fine-needle lung aspirate • immunocompromised patient • invasive radiology • lung cancer • transthoracic needle aspiration


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Transthoracic fine-needle aspiration (FNA) of the lung is established as a diagnostic tool in the evaluation of localized pulmonary lesions, particularly nodules and masses. The sensitivity of FNA for detecting malignancy has been shown to be 84 to 88%, with specificity close to 99%.1 The role of FNA in determining infectious pathogens is less well studied, although reports of community-acquired pneumonia and pneumonia in children suggest that bacterial pathogens can be obtained.2 3 The role of FNA in the immunocompromised patient where pulmonary complications are very common and where opportunistic as well as usual infections, inflammatory disorders, and cancers are all found has not been well studied. Bronchoscopy with BAL is often the first diagnostic technique employed in this group of patients, particularly when diffuse infiltrates are present. However, FNA avoids contamination of culture material by upper respiratory tract flora, and may be more useful when focal radiographic abnormalities are present. The use of FNA has been limited in the immunocompromised patients, in part by concern for bleeding complications in those with abnormal hematologic profiles. To better clarify the role and safety of FNA in the immunocompromised patient, we undertook this review of our experience with FNA at Memorial Sloan Kettering Cancer Center in patients with hematologic malignancy.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Patients
Patients who underwent FNA of the lung were identified by retrospective review of the Memorial Sloan Kettering Cancer Center Interventional Radiology (IR) procedure database from January 1, 1991, to June 30, 1999. Patients were included if they had (1) an FNA for diagnosis of a pulmonary parenchymal abnormality of unknown etiology, and (2) an underlying hematologic malignancy, or bone marrow transplantation (BMT) for a hematologic malignancy. Patients were excluded if there was only a remote history of hematologic malignancy (at least 10 years in remission) or if nonparenchymal lung lesions, such as lymph nodes, mediastinal masses, or pleural abnormalities, were found in biopsy specimens.

Data
Data were collected from the electronic chart on type of hematologic malignancy and transplant, pulmonary symptoms, chest radiographic findings, laboratory values at the time of biopsy, diagnostic procedures other than FNA, results of the FNA, complications of the procedure, and final outcome.

Definitions
Radiographic findings were classified as nodules if the lesions were round and <= 2 cm, masses if > 2 cm, cavities if masses with necrosis, and infiltrates if ill-defined parenchymal opacities were seen. Neutropenia was a neutrophil count of <= 1,000/µL. Thrombocytopenia was a platelet count of < 50,000/µL. Coagulopathy was considered present if the prothrombin time (PT) was >= 15 s, international normalized ratio (INR) was >= 1.5, and/or partial thromboplastin time (PTT) was >= 40 s. Infection was considered to be diagnosed if an organism was identified in either stain or culture findings. Inflammatory changes were cellular changes not meeting criteria for malignancy and in which no evidence of infection was found.

Complications
Complications included pneumothorax, need for chest tube placement, and bleeding. The latter included hemoptysis and hemothorax.

FNA Technique
The decision to perform FNA of a focal lung lesion was made by the attending physician caring for the patient in collaboration with an interventional radiologist, often in consultation with the pulmonary service. Based on laboratory parameters obtained the day of the procedure, patients with platelet counts < 20,000/µL received 6 U of platelets prior to the procedure, and another 6 U were administered in the IR department during the procedure. If the platelet count was between 20,000/µL and 50,000/µL, only 6 U were administered in the IR suite at the time of biopsy. Patients with an INR > 2.0 received 2 U of fresh frozen plasma, one on the floor and the other in the IR suite at the time of biopsy. Patients with INR between 1.5 and 2.0 received only 1 U of fresh frozen plasma in the IR suite at the time of biopsy.

Biopsies were performed using local anesthesia and real-time fluoroscopic guidance, with a cytotechnologist in attendance to examine a sample of the aspirate immediately after it was obtained. Fluoroscopy was preferred for all cases, if possible. If adequate diagnostic material was evident following the first needle aspirate, the procedure was terminated. If inflammatory material was seen, but without a definite pathogen, a second aspirate was usually obtained in an effort to avoid sampling error. If the initial specimen was unsatisfactory, or contained only "normal site tissue," the procedure was repeated. Occasionally when small lesions were being sampled, perilesional hemorrhage might obscure the lesion, precluding a second aspirate.

All procedures were performed using 22-gauge needles. If a diagnosis of malignancy was obvious on initial review of the aspirate, then cultures were not routinely sent. In all other cases, specimens were submitted for Gram’s stain as well as bacterial, fungal, viral, and mycobacterial cultures, in addition to a cytopathologic study.

Chest fluoroscopy or postbiopsy CT scanning were performed at the conclusion of each biopsy. An immediate upright chest radiograph was then obtained. Patients recovered in a monitored setting until in clinically stable condition to be discharged. Charts on clinical follow-ups were reviewed.

Statistics
Statistical analysis was done using {chi}2-Independence with GB-STAT software (Dynamic Microsystems; Silver Spring, MD).


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Sixty-seven patients underwent a total of 71 FNAs. Their mean age was 49 years (range, 11 to 87 years). The patient characteristics and clinical presentation are shown in Table 1 . The most common underlying malignancy was lymphoma, which was present in 63% of the patients. Of the 58 cases in whom medical records were adequate to assess clinical presentation, 79% had symptoms, while the remaining 21% were asymptomatic and had only radiographic abnormalities. Thrombocytopenia was present in 8% of patients, and coagulopathy was present in 10% of patients.


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  		Table 1.. Patient Characteristics*

 
The yield of FNA in our patients for detecting a specific abnormality (infection or malignancy) was 56% (40 of 71 FNAs). This included 30 specimens in which malignancy was demonstrated and 10 specimens in which infection was found (Table 2 ). In another 11 patients, inflammatory changes were found but were considered adequate results by the clinician with no further procedure or intervention performed. Thus, the FNA produced a clinical answer in a total of 51 patients for a total diagnostic yield of 72%. Additional diagnostic procedures were performed in 18 patients (25%), and the final diagnosis was established by clinical course in two cases. The additional procedures were open-lung biopsy in 13 patients, bronchoscopy followed by open-lung biopsy in 3 patients, and repeat FNA in 2 patients. As a result of the additional procedures, cancer was found in an additional nine patients, infection in an additional five cases, and inflammatory changes were confirmed in six cases. Before undergoing FNA of the lung, 18 patients had undergone bronchoscopy (only 1 patient had undergone transbronchial biopsy) with negative findings.


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  		Table 2.. Diagnostic Yield of FNA*

 
Comparing the results of needle aspirate to the diagnosis ultimately established, the sensitivity of FNA in hematologic malignancy for finding cancer was 77% (30 of 39 FNAs), with 90% yield (9 of 10 FNAs) for lung cancer, and 68% yield (21 of 31 FNAs) for lymphoma (Table 2) . All 30 patients with diagnostic needle aspirates for malignancy had underlying lymphoma. When infection was present, 67% (10 of 15 FNAs) were correctly diagnosed with two cases of Cryptococcus, one case of cytomegalovirus, and one bacterial infection missed (Table 2) . There was one case in which a bacterial pathogen was found by FNA but not believed, and patient proceeded to open-lung biopsy, which confirmed the diagnosis. All three cases of invasive pulmonary aspergillus were diagnosed by FNA.

The radiographic patterns seen were nodules in 26 patients (37%), a mass in 26 patients (37%), focal infiltrates in 15 patients (21%) and cavitary lesions in 4 patients (5%). The lesions were present in the right lung in 42 patients (59%) and in the left lung in 29 patients (41%). Distribution by specific pulmonary lobe was right upper lobe (17%), right middle lobe (8%), right lower lobe (34%), left upper lobe (20%), and left lower lobe (21%). There was no significant statistical relationship between the yield and the radiographic pattern (Table 3 ). A specific infection or malignancy was found with FNA in 62% of those with nodules (16 of 26 patients), 58% of those with masses (15 of 26 patients), 47% of those with infiltrates (7 of 15 patients), and 50% of those with cavities (2 of 4 patients). FNA was performed under fluoroscopic guidance in 52 patients (73%), and under CT guidance in 19 patients (27%). Fluoroscopy-guided FNA established a specific cause in 58% (30 of 52 patients) and CT-guided FNA established a specific cause in 52% (10 of 19 patients), which were not significantly different.


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  		Table 3.. Diagnostic Yield of FNAs Based on the Radiographic Presentation, Location of Lung Lesion, and Technique Used*

 
Complications occurred in 18 patients (25%; Table 4 ). Pneumothorax occurred in 14 cases (20%), with four patients (6%) requiring chest tube placement. Bleeding complications, most of which were mild, occurred in six patients (8%), but there was one death related to bleeding. Hemoptysis, which was mild to moderate, occurred in five patients, one of whom also had a pneumothorax develop. There were two patients with hemothorax, of whom one required chest tube placement. The overall risk of complications was increased in those with thrombocytopenia or abnormal coagulation parameters. The patient who died had thrombocytopenia, with a rapidly dropping platelet count in the days before the procedure, and coagulopathy.


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  		Table 4.. Complications in FNAs*

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Transthoracic FNA of the lung is an effective technique for sampling focal peripheral lung lesions.1 This diagnostic technique has been used most often for determining the diagnosis of malignancy in nodules or masses in normal hosts. Experience with FNA to determine the presence of either infection or cancer in immunocompromised patients has been less frequently studied. Castellino and Blank4 in 1979 found a diagnostic yield of 73% with FNA in 82 immunocompromised patients. Most of the patients were heart or kidney transplant recipients, but 12 patients had leukemia or lymphoma. Bacterial infection, including nocardia, was found in 26 patients, and fungal infection was found in 23 patients; none of these patients had cancer. Limited hemoptysis occurred in 3% of cases and pneumothorax in 26% of cases, with half of these patients requiring a chest tube. Crawford et al5 found a yield of 67% with FNA in 16 BMT recipients with focal radiographic lesions. Most had fungal infections, and complications occurred in 15% of patients. More recently, Hwang et al6 reported on use of FNA in 21 immunocompromised patients, of whom 9 patients had a hematologic malignancy. The yield of FNA was 66% in patients with hematologic malignancy with bacterial and fungal infections being detected. Only one small pneumothorax was reported. There have also been several reports on use of FNA in patients infected with HIV, where yields of 62 to 84% were found.7 8

We undertook a study of FNA in hematologic patients because this group is at risk for a wide variety of pulmonary problems, and abnormal hematologic parameters are often present, making diagnostic procedures more difficult. In our study of 71 FNAs performed in 67 patients with hematologic malignancies, FNA provided a specific diagnosis (either cancer or infection) in 56% of cases. In an additional 11 cases (16%), inflammatory disorders were found that were accepted by clinicians without the need for further testing, for an overall diagnostic yield of 72%. As is the case for immunocompetent patients, the yield for lung cancer in this population was high (90%). The ability to diagnosis lymphoma was less predictable but still had a yield of 68%. In our series, all patients with pulmonary lymphoma had known lymphoma, which may have facilitated determining this diagnosis from limited material from the needle aspirate. The yield for infection in our series of 67%, which is similar to what has been previously reported, and also compares favorable to that of bronchoscopy in patients with hematologic malignancy. Of note, however, the types of infections found were predominately fungal or bacterial, for which bronchoscopy does not have a high yield.9

The choice of a diagnostic procedure in an immunocompromised patient must be based on the yield for the most likely pathogens and the safety of the procedure in the circumstances. Although bronchoscopy has an excellent yield for diffuse diseases, such as Pneumocystis carinii and cytomegalovirus infection, the yields with fungal infection has been lower, in the range of 50%.9 These likely reflect the more focal nature of these latter processes, where FNA has the advantage because the specimen can be obtained directly in the radiographically abnormal area. This is particularly important in establishing the diagnosis of cancer in a nodular density. Another advantage of FNA is that uncontaminated specimens are obtained for microbiologic analysis, as opposed to bronchoscopy, where specimens are contaminated because the scope passes through the upper airway. Thus the significance of recovery of some pathogens, such as bacteria or Candida species can be more correctly interpreted.

Inflammatory disorders are increasingly being recognized as a cause of pulmonary abnormalities in immunocompromised patients. They were the most common type of abnormality found at open-lung biopsy at our institution for undiagnosed lesions in patients with hematologic malignancy and represent 24% (17 of 71 FNAs) of the ultimate diagnoses in the current series.10 The finding of an inflammatory disorder at FNA presented a diagnostic dilemma as it does when this type of abnormality is found by transbronchial biopsy. Of the 17 cases in our series, one third of these patients went on to further procedures to clarify the diagnosis.

For performing FNA, fluoroscopy is preferred at our institution to CT guidance as long as the lesion can be targeted. Nodules as small as 4 to 5 mm can often be located. Fluoroscopy is a real-time modality, and needle placement is quicker and more accurate. The longer the needle is in the patient, the higher the potential risk of pneumothorax. CT guidance can be a problem in patients for whom following breath-holding instructions is difficult. Accurate targeting with CT requires the lesion to remain in the same axial plane when the biopsy needle is inserted as it was when the lesion was localized. CT guidance is used for small pleural-based plaque-like lesions that are not visible en face, or ill-defined infiltrates that were seen only on the lung windows of the CT and could not be visualized on the soft-tissue window. In this study, fluoroscopy was used in 73% of cases, with a similar diagnostic yield to CT guidance.

The complication rate for pneumothorax in our series was similar to that reported11 with FNA in immunocompetent patients. Bleeding did occur in 8% of patients but was not a significant clinical problem in most cases, although one death did occur. The overall risk of bleeding complications was not correlated with the number of platelets present, but only 8% of the patients had platelet counts < 50,000/µL and all received platelet transfusions. The one death occurred in a patient with both coagulopathy and a rapidly dropping platelet count. This case raises caution about such a combination of hematologic abnormalities and the need for very aggressive transfusion and follow-up assessments. We now repeat platelet counts on the day of the procedure in any patients with rapidly changing clinical parameters.

Pneumothorax and pulmonary hemorrhage are known complications of FNA that have limited the use of this technique in patients with respiratory distress or failure where a pneumothorax cannot be tolerated, or in cases of severe hematologic abnormalities where the risk of bleeding is high.11 Bronchoscopy with transbronchial biopsy is also limited in such situations. BAL, however, has been safely performed in patients requiring mechanical ventilation and those who are thrombocytopenic or with a coagulopathy, making it a preferred procedure for those with severe respiratory distress or with marked coagulopathy or severe thrombocytopenia.

In summary, we found that FNA has a good overall yield for the diagnosis of focal radiographic lesions in patients with hematologic malignancy. The accuracy of determining lung cancer was excellent, and FNA was also useful for confirming the presence of lymphoma in nodular densities, although this was not as reliable as finding lung cancer. As had been noted in prior studies, FNA has a yield for the detection of infections that compares favorably to bronchoscopy in this setting, although the type of infections were usually fungal, bacterial, or mycobacterial. The procedure was safely performed even in this high-risk group of patients with the same risk of pneumothorax as in the general population. Bleeding complications are a concern in coagulopathic and thrombocytopenic patients, and careful patient selection and monitoring is necessary. We conclude that FNA should be considered a useful tool for evaluating focal pulmonary abnormalities in patients with hematologic malignancies.


   Footnotes
 
Abbreviations: BMT = bone marrow transplantation; FNA = fine-needle aspiration; INR = international normalized ratio; IR = interventional radiology; PT = prothrombin time; PTT = partial thromboplastin time

Received for publication March 14, 2001. Accepted for publication July 12, 2001.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Lacasse, Y, Wong, E, Guyatt, GH, et al (1999) Transthoracic needle aspiration biopsy for diagnosis of localized pulmonary lesions: a meta-analysis. Thorax 54,884-893[Abstract/Free Full Text]
  2. Ruiz-Gonzalez, A, Falguera, M, Nogues, A, et al (1999) Is Streptococcus pneumoniae the leading cause of pneumonia of unknown etiology? A microbiologic study of lung aspirates in consecutive patients with community-acquired pneumonia. Am J Med 106,385-390[CrossRef][ISI][Medline]
  3. Berger, R, Arango, L (1985) The value and safety of percutaneous lung aspiration for children with serious pulmonary infections. Pediatr Pulmonol 1,309-313[Medline]
  4. Castellino, RA, Blank, N (1979) Etiologic diagnosis of focal pulmonary infection in immunocompromised patients by fluoroscopically guided percutaneous needle aspiration. Radiology 132,563-567[Abstract]
  5. Crawford, SW, Hackman, RC, Clark, JG (1989) Biopsy diagnosis and clinical outcome of persistent focal pulmonary lesions after marrow transplantation. Transplantation 48,266-271[ISI][Medline]
  6. Hwang, SS, Kim, HH, Park, SH, et al (2000) The value of CT-guided percutaneous needle aspiration in immunocompromised patients with suspected pulmonary infection. AJR Am J Roentgenol 175,235-238[Abstract/Free Full Text]
  7. Klein, JS, Salomon, G, Stewart, EA (1996) Transthoracic needle biopsy with a coaxially placed 20-gauge automated cutting needle: results in 122 patients. Radiology 198,715-720[Abstract/Free Full Text]
  8. Hung, CC, Chen, MY, Kuo, PH, et al (1999) Ultrasound-guided percutaneous transthoracic needle aspiration biopsy for diagnosis of pulmonary lesions in advanced HIV infection. J Formos Med Assoc 98,195-200[ISI][Medline]
  9. Baughman, RP (1994) Use of bronchoscopy in the diagnosis of infection in the immunocompromised host. Thorax 49,3-7[ISI][Medline]
  10. White, DA, Wong, PW, Downey, R (2000) The utility of open lung biopsy in patients with hematologic malignancies. Am J Respir Crit Care 161,723-729[Abstract/Free Full Text]
  11. Poe, RH, Kallay, MC, Wicks, CM, et al (1984) Predicting risk of pneumothorax in needle biopsy of the lung. Chest 85,232-235[Abstract/Free Full Text]



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