CT-Guided Percutaneous Core Needle Biopsy of Small Pulmonary Nodules (< 2 cm): How Efficient is it as a Diagnostic Tool in Ruling Out Metastatic Disease?

Abstract

Introduction

Incidentally detected small pulmonary nodules in patients with an underlying malignancy most often warrant sampling. Biopsy from such small pulmonary nodules (< 2 cm) is challenging. In this study, we aim to evaluate the accuracy of computed tomography (CT)-guided percutaneous core needle biopsy (CNB) of small pulmonary nodules.

Materials and Methods

A total of 169 patients who had CT-guided percutaneous CNB for small pulmonary nodules (less than 2 cm) between January 2015 and December 2018 were the subjects of this retrospective, single-center investigation. We determined the success rate of CNB and the rate of a diagnostic biopsy. Calculations were made for a multivariate study of the risk variables for complications, such as pneumothorax and pulmonary hemorrhage.

Results

The success rate of lung biopsy, defined by obtaining a sample of pathologically reportable quality, was 92.9% (157/169). A malignancy was diagnosed in 60.4% of cases (102/169). Pneumothorax developed in 21.9% cases (37/169), with only 5.3% (9/169) patients requiring treatment (8 needle aspirations and 1 pigtail catheter drainage). Use of a thicker (18G) biopsy needle was the only statistically significant predictor of pneumothorax (odds ratio 2.61, 95% confidence interval 1.24–5.51, p = 0.01). Perifocal hemorrhage was common (72.2%, 122/169) but clinically significant pulmonary lobar hemorrhage was seen only in 6.5% of the cases (11/169). One patient required intensive care unit admission due to desaturation from aspiration of blood.

Conclusion

CT-guided biopsy of small pulmonary nodules is safe and feasible with a good success rate.

 

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Keywords

CT-guided biopsy - lung metastasis - small pulmonary nodules

Introduction

Transthoracic biopsy plays an important role in the diagnosis and staging of primary lung cancer.[1] Indeterminate lung nodules on imaging in patients with known malignancy need sampling to rule out any underlying metastatic foci, especially when curative options are considered.[2] [3] However, biopsy from lung lesions smaller than 2 cm in size is a challenging task. In spite of availability of endobronchial biopsies (EBBs) and video-assisted thoracoscopic (VATS) biopsies, computed tomography (CT)-guided transthoracic biopsy remains the preferred method of choice for such smaller lesions.[3] CT biopsy has advantages over VATS and lobectomy since it is less invasive. Compared to the EBB, the CT-guided biopsy samples are bigger. Core needle lung biopsy is preferred over fine-needle aspiration cytology because of its higher diagnostic accuracy in case of nonmalignant etiology, better tissue characterization, and option of additional staining with immunohistochemistry markers for confirmation of malignant lesions.[4] [5] [6] The reported diagnostic accuracy of CT-guided core biopsy is 62 to 97% in lesions larger than 2 cm.[7] Successful core biopsy of smaller lesions remains challenging, especially when the lesions are situated in the lower lobe. There is concern for increased rate of complications as the size of the lesion decreases. The primary aim of this study was to report the diagnostic accuracy and rate of complications of CT-guided transthoracic core biopsy of pulmonary nodules measuring less than 2 cm in long-axis diameter. The secondary aim was to identify risk factors associated with clinically significant postprocedure complications, including pneumothorax and pulmonary hemorrhage.

 

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Materials and Methods

This study was a retrospective chart review and the necessity for an informed consent was waived by the Institutional Review Board. Between January 2015 and December 2018, we collected data on consecutive CT-guided core lung biopsies on 169 patients who had a solitary lung lesion smaller than or equal to the size of 2 cm. Repeat biopsies were not included. The biopsies were performed by two interventional radiologists with a minimum of 2 years of experience with CT-guided biopsy. The clinical decision to perform a biopsy was made by the referring physicians and the feasibility and approach of the biopsy were determined by the interventional radiologists. All biopsies were performed as a daycare procedure. Informed procedural consent was obtained from the patient and one first-degree relative prior to the biopsy procedure. The prothrombin time-to-international normalized ratio (PT-INR) and platelet count were checked before the biopsy procedure. Necessary corrections were made before the procedure in patients with PT-INR > 1.5 and platelet count < 50,000/mm³.

Biopsies were performed using two different 64-slice scanners (Discovery, General Electric and Biograph, Siemens Medical Systems). The prebiopsy CT images of the patients were reviewed to determine the patient position during the biopsy. The patient was transferred to the CT table and placed in a predetermined position. The safest and most accessible path for the biopsy needle was selected to avoid bones, large vessels, and blebs/bullae. Fissures were avoided as much as possible. After taking all aseptic precautions, approximately 10 mL of 2% lignocaine was injected into the skin and subcutaneous tissue for local anesthesia. All the biopsies were performed using the coaxial method (17-gauge introducer needle with 18G automatic biopsy needle and 19G coaxial introducer with 20G automatic biopsy needle). Patients were instructed not to take deep breaths. Under free breathing, the coaxial needle was introduced. Once the position of the tip of the coaxial needle was deemed satisfactory, the inner stylet was removed, and multiple tissue cores (minimum 2) were taken using an automatic biopsy gun. CT fluoroscopy was not available in our institute. The number of samples varied and that depended on the quality of the sample, bleeding, and the patient's condition. All tissue samples were preserved in a 10% formaldehyde solution. Additional tissue cores were preserved in normal saline where infective etiology was a differential diagnosis for the pulmonary nodule under evaluation. A check CT scan was performed at the end of the procedure to rule out pneumothorax or pulmonary hemorrhage. All patients were observed for at least 2 hours in the recovery ward after the biopsy.

Individualized treatment decisions were made for any patient who developed a pneumothorax depending upon the volume of air and the general condition of the patient. Patients with small pneumothorax were monitored with a follow-up CT after 1 hour to check for progression of the pneumothorax. Asymptomatic, small, and stable cases were not treated. Enlarging or large pneumothoraces were treated with aspiration alone, if asymptomatic, and with pigtail catheter insertion, if symptomatic. All symptomatic pneumothoraces were treated with an 8F pigtail catheter insertion and drainage to a water-seal bag. All patients with pneumothorax were reviewed after 24 hours with a chest radiograph. In patients with pigtail drainage, after the radiograph showed complete lung expansion, the pigtail tube was removed after clamping for 24 hours.

The severity of lung hemorrhage was divided into four grades. Grade 0 was defined as no pulmonary hemorrhage, grade 1 as needle tract or perfocal hemorrhage < 2 cm in width, grade 2 as hemorrhage > 2 cm in width but sublobar, and grade 3 as lobar hemorrhage or greater, and grade 4 as hemothorax[8] ([Fig. 1]). Patients who had minor hemoptysis received conservative care. Patients with moderate to large hemoptysis were admitted and given treatment based on the severity of their symptoms. Intravenous tranexamic acid was administered to patients with mild to moderate desaturation along with oxygen support. On the basis of merit, patients with gross desaturation were intubated.

Fig. 1 Grades of hemorrhage. (A, C, and E) Axial computed tomography (CT) sections showing lesions (arrows) before biopsy. (B, D, and F) Postbiopsy images showing grade 1, 2, and 3 hemorrhages, respectively (curved arrow).

The technical success of core needle biopsies (CNBs) was defined by availability of a conclusive pathological diagnosis, either benign or malignant. CNB was deemed unsuccessful if the pathology report was inconclusive due to a suboptimal or inadequate sample. Data was collected regarding the final diagnosis (benign vs. malignant) of the successful biopsies. Final diagnosis of the lesion was determined by either final pathology (in malignant) or follow-up imaging (in biopsies that were negative for malignancy but showed nonspecific benign findings). CNB findings of malignancy were considered true positives if the histopathological findings were consistent with the known primary malignancy or the subsequent clinical course was consistent with malignancy. Malignant CNB findings were considered false positives when the subsequent clinical course was inconsistent with malignancy or the surgical specimen contradicted the initial biopsy specimen's histopathological finding. Benign CNB findings were considered true positives when the lesion disappeared or decreased in size with or without antibiotics or the lesion remained stable for at least 1 year after biopsy or there was surgical confirmation. Benign CNB findings were considered false positives when the subsequent clinical course was inconsistent with a benign diagnosis or surgical findings showed malignancy. The inadequate or paucicellular CNB specimens were considered false negatives and none of the lesions were classified as true negatives. Lesion size, location (relation to pleura, lower lobe vs. nonlower lobe, central vs. peripheral), presence of emphysema or fibrosis in background lung, patient position (prone vs. supine), needle size (18G vs. 20G), and needle path (90 degrees to pleura vs. oblique) were recorded. Number and degree of pulmonary hemorrhage and pneumothorax were recorded. Factors predicting clinically significant pneumothorax and hemorrhage were examined by statistical analysis.

 

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Results

A total of 169 nodules were biopsied (32–80 years) ([Table 1]). Size of the nodules ranged from 0.5 to 2.0 cm (average 1.4 ± 0.4 cm). The pathologically reportable quality biopsy samples (success rate) were obtained in 92.9% (157/169) cases and pathological inadequate or nondiagnostic results were obtained in 7.1% (12/169) cases. The success rate for lesions larger than > 1 cm was 97.1% (101/104) and for subcentimeter lesions it was found to be 86.2% (56/65).

Table 1 Patient characteristics, lesion variables, and procedure variables

Age (mean)	59
Sex
Male	140
Female	29
Complications
Pneumothorax	37/169 (21.9%)
Hemorrhage	149/169 (88%)
Grade 1	122 (72.2%)
Grade 2	16 (9.5%)
Grade 3	11 (6.5%)
Minor hemoptysis	4
Major hemoptysis	1

Malignant disease was reported in 60.4% (102/169) and benign pathologies were noted in 32.5% (55/169) cases ([Table 2]). Malignancy was reported in 82 lesions that were larger than 1 cm and 20 lesions less than 1 cm. A size cutoff value of 1 cm for diagnosis of malignancy yielded a sensitivity of 80%, specificity of 44.7%, accuracy of 66%, positive predictive value of 68.9%, and negative predictive value of 60%. Average size of malignant lesions was significantly larger (1.49 ± 0.4 cm, median 1.5 cm); however, there was significant overlap between the groups. Average size comparison between benign, malignant, and indeterminate lesions is given in [Table 3] Pneumothorax was seen in 21.9% cases (37/169) ([Tables 4] and [5]). Out of 37 patients who developed pneumothorax, only 5.3% (9/169) patients required treatment (8 needle aspirations, 1 pigtail catheter drainage). Grade 1 or perifocal hemorrhage was common (72.2%, 122/169), but clinically significant grade 3 pulmonary lobar hemorrhage was seen only in 6.5% cases (11/169). One patient required intensive care unit (ICU) admission due to desaturation from aspiration of blood. Note that 11.8% cases (20/169) had no hemorrhage and 9.5% cases (16/169) had grade 2 or sublobar hemorrhage. No patient developed hemothorax ([Tables 6] and [7]). No significant association of hemorrhage was observed with location, size of the needle used, or size of the lesion.

Table 2 Histopathology findings

Malignant	102
Benign	55
Fungal infection	1
Organizing pneumonia	5
Caseating granuloma	4
Noncaseating granuloma	32
Other nonspecific chronic inflammation	12
Hamartoma	1
Inconclusive	12
Total	169

Table 3 Relationship between the diagnostic accuracy and size

	Indeterminate (Group 1)	Benign (Group 2)	Malignant (Group 3)
Number [percentage]	12.0 [7.1]	55.0 [32.5]	102.0 [60.4]
Average size (cm) [mean ± SD (SE)]	1.01 ± 0.4 (0.12)	1.31 ± 0.45 (0.06)	1.49 ± 0.4 (0.04)
Median [IQR]	0.95 (0.7–1.15)	1.2 (0.9–1.75)	1.5 (1.2–1.9)

Abbreviations: ANOVA, analysis of variance; IQR, interquartile range; SD, standard deviation; SE, standard error.

Note: One-way ANOVA: F statistic = 8.93 [p = 0.0002].

Table 4 Incidence of pneumothorax and variables

Explanatory factor	Pneumothorax (n = 37)	%	No pneumothorax (n = 132)	%
Subcentimetric	15	40.5	50	37.9
Not subcentimetric	22	59.5	82	62.1
Lower lobe	20	54.1	50	37.9
Not lower lobe	17	45.9	82	62.1
Abnormal lung	8	21.6	15	11.4
Normal lung	29	78.4	117	88.6
18G needle	19	51.4	38	28.8
20G needle	18	48.6	94	71.2
Prone position	25	67.6	67	50.8
Supine position	12	32.4	65	49.2
> 90 angle of needle	16	43.2	65	49.2
< 90 angle of needle	21	56.8	67	50.8
Subpleural nodule	13	35.1	40	30.3
Not subpleural	24	64.9	92	69.7
Central nodule	2	5.4	21	15.9
Peripheral nodule	35	94.6	111	84.1
Fissure in needle path	3	8.1	18	13.6
No fissure	34	91.9	114	86.4

Table 5 Multivariate analysis of explanatory factors predicting postbiopsy pneumothorax

	Odds ratio (95% CI)	p-Value
Subcentimetric nodule	3.62 [1.40–9.33]	0.00777**
Lower lobe location	2.97 [1.01–8.74]	0.0485*
Background lung disease (emphysema, ILD)	3.01 [1.00–9.04]	0.0493*
Use of 18G needle	3.52 [1.52–8.16]	0.00334**
Prone position	0.81 [0.28–2.36]	0.695
Oblique needle angle	1.64 [0.71–3.81]	0.251
Subpleural location	1.07 [0.45–2.55]	0.887
Fissure in needle path	0.98 [0.25–3.87]	0.971

Abbreviations: CI, confidence interval; ILD, interstitial lung disease.

Note: ** Statistically significant.

Table 6 Incidence of significant pulmonary hemorrhage with other variables

Explanatory factor	No hemorrhage (n = 20)	%	Hemorrhage (n = 149)	%
Subcentimetric	1	5.0	31	20.8
Not subcentimetric	19	95.0	118	79.2
Lower lobe	7	35.0	63	42.3
Not lower lobe	13	65.0	86	57.7
Abnormal lung	2	10.0	21	14.1
Normal lung	18	90.0	128	85.9
18G needle	3	15.0	54	36.2
20G needle	17	85.0	95	63.8
Prone position	11	55.0	81	54.4
Supine position	9	45.0	68	45.6
> 90 angle of needle	10	50.0	76	51.0
< 90 angle of needle	10	50.0	73	49.0
Subpleural nodule	4	20.0	49	32.9
Not subpleural	16	80.0	100	67.1
Central	0	0.0	23	15.4
Peripheral	20	100.0	126	84.6
Pneumothorax	2	10.0	35	23.5
No pneumothorax	18	90.0	114	76.5

Note: There was no statistically significant correlation with variables.

Table 7 Relationship of chance of clinically significant hemorrhage and different factors

	OR	95 CI	z	p
Subcentimetric	2.01	0.59–6.89	1.12	0.26
Lower lobe	1.36	0.40–4.65	0.49	0.62
18G gun	0.72	0.18–2.83	0.47	0.64
Prone	0.29	0.07–1.14	1.78	0.08
Supine	3.44	0.88–13.45	1.78	0.08
Subpleural	1.27	0.36–4.54	0.37	0.71
Peripheral	1.62	0.20–13.27	0.45	0.65
< 90	0.75	0.22–2.57	0.45	0.65
Fissure in path	1.62	0.33–8.10	0.59	0.55

Abbreviations: CI, confidence interval; OR, odds ratio.

Note: There was no statistically significant correlation with location, size, needle size, or patient position.

Pneumothorax was more common with the use of a 17G coaxial needle and an 18G biopsy needle (odds ratio 2.61, 95% confidence interval 1.24–5.51, p = 0.01) ([Tables 4] and [5]). Pneumothorax was also more common when the patient was placed in a prone position; however, this was not found to be statistically significant. No statistically significant correlation of development of pneumothorax with location or size of the lesion was noted.

Except for one nondiagnostic sample that turned out to be malignant, all pathologically benign and nondiagnostic samples showed benign course during follow-up. No false positive cases were detected in our series. If we assume nondiagnostic samples as negative for malignancy (as happens in normal practice), the overall sensitivity of CT-guided biopsy for small lung nodules was 99% and specificity was 100%.

 

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Discussion

CT scan is the work horse in the diagnosis and staging of multiple neoplastic lesions resulting in an increased detection of smaller lung nodules that are suspicious for metastases. Biopsy even in suspected metastatic disease is important, since in the presence of oligometastatic disease, treatment with curative intent can be considered.[9] [10]

Accuracy of CT-guided biopsy is well documented in the literature; however, the same is not established for smaller lesions, that is, lesions smaller than 2 cm.[11] These lesions are technically difficult to target, which may result in increased risk of complications such as pneumothorax and pulmonary hemorrhage. In the present study, attempts were made to address these issues.

The present study shows the overall success rate of CT-guided biopsy for obtaining diagnostic quality tissues from < 2 cm lesion is 91.6%, which falls in the range of accuracy reported for lung lesions in general.[11] [12] This suggests that the accuracy of CT-guided biopsy is not greatly influenced by smaller sized lesions. Interestingly, the diagnostic accuracy of CT-guided biopsy for subcentimeter-sized lesions is not greatly different from lesions measuring 1 to 2 cm in size (86% vs. 97%, respectively).

In our series, the size of the smallest lesion that was biopsied was 5 mm and that of the largest was 2 cm. Nondiagnostic biopsy was reported in 7.1% (12) of the cases. Majority (75%, 9 out of 12) of nondiagnostic biopsies were reported from lesions that measured less than a centimeter. Interestingly, the majority (83.3%, 10 out of 12) of nondiagnostic biopsies turned out to be benign diseases on follow-up and only two cases turned out to be malignant.

Only 40% (20/50) of lesions less than 1 cm turned out to be malignant in contrast to 68.9% (82/119) of lesions > 1 cm that turned out to be malignant. This finding may suggest the larger the size of the lesion, the higher the chances of malignancy ([Table 8]).

Table 8 Group comparison of diagnostic accuracy with size

	Nondiagnostic	Benign	Malignant
Subcentimetric (n = 65)	9.0 (13.8%)	29.0 (44.6%)	27.0 (41.5%)
Not subcentimetric (n = 104)	3.0 (2.9%)	26.0 (25%)	75.0 (72.1%)

Note: Mann–Whitney U test [two-tailed]: U = 2273, z score = 3.57 (p = 0.00034). There is no statistically significant association between diagnostic accuracy and lesion size.

Except for one case, where a nondiagnostic report on pathology turned out to be malignant on subsequent follow-up, the rest of the biopsy reports were consistent with clinical course of the disease. Unlike larger lesions, while performing biopsy from a lesion less than 2 cm in size, the entire lesion is likely to be sampled thus leaving very little scope for sampling errors. This can explain the high accuracy of the pathological biopsy reports.

Though the rate of occurrence of pneumothorax was higher (21.9%), patients who actually required any active intervention were only 5.3% of the cases. Majority of pneumothoraces were minor and stable, which were successfully managed conservatively. Higher rate of pneumothorax most likely reflects the difficulty in targeting the lesion.[13] Larger gauge needles were associated with statistically significant pneumothorax compared to smaller needles. No statistical significance could be demonstrated with respect to location of the lesion (central or peripheral and upper or lower lobe, or position of the patient).[14] Even though in our series the presence or absence of emphysema did not influence the occurrence of pneumothorax, it is a safe practice to avoid the emphysematous areas along the pathway of the needle.

Pulmonary hemorrhage was found to be very common (88%); however, most of them were either tract hemorrhages or focal pulmonary hemorrhages not requiring any significant intervention or management ([Fig. 1]). Grade 3 hemorrhage was seen in 6.5% cases (11/169). Two percent (4/169) had self-limiting mild hemoptysis, which required no treatment. One patient had significant hemoptysis who required ICU admission for 2 days. Unlike previous studies, no statistical significance could be demonstrated between the occurrence of hemorrhage with the site of the lesion, position of the patient, and gauge of the needle in our study.[14]

Targeting small pulmonary lesions can more often than not be very challenging. Lesions located in the upper lobe are relatively easily targeted as compared to lower lobe lesions, which tend to move with respiration.[15] Meticulous preprocedure planning plays a very important role for a successful biopsy. Performing all manipulations in the biopsy gun in terms of site of entry and angulation before piercing the pleura may help in significantly reducing complications.[15] The moving target may require extremely slow advancement of needle and manipulation of the needle at each step toward the direction of the lesion. Appropriate biopsy throw length needs to be selected keeping in mind not to unnecessarily sample normal lung parenchyma beyond the lesion. Extra care needs to be taken about throw length when the lesion is in close proximity to pulmonary vessels and bronchus as bleeding and aspiration into the bronchus can be catastrophic.

Subpleural lesions in particular pose a challenge since these lesions tend to be highly mobile with respiration and coaxial needle stability cannot be achieved within them. It is thus preferred to approach such lesions close to the pleura tangentially for better coaxial needle stability rather than taking direct short distance approach, which may result in increasing chances of shearing of the pleura ([Fig. 2]).[15]

Although positron emission tomography (PET)/CT is better than conventional CT in detecting bony metastasis, the sensitivity and specificity of PET/CT for pulmonary lesions in excluding metastasis are roughly 79 and 81.8%, respectively. The significant prevalence of well-known low 18F-fludeoxyglucose-avid tumors and the small nodule sizes were the main causes of false negative PET/CT results.[16]

Limitation of our study includes small sample size and its retrospective nature. Negative sample may not always imply nonmalignant lesions. Sampling error can happen especially when these lesion are too small to target due to technical reasons. Though we included patients with known malignancy, these findings can be generalized to other populations.

 

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Conclusion

CT-guided biopsy of small pulmonary nodules is safe and feasible with good accuracy. Adequate samples can be obtained in most cases. Majority of the complications are minor, which do not require any intervention. In a patient with a known malignancy, a lung nodule may indicate nonmetastatic disease in significant number of patients, necessitating biopsy confirmation.

Fig. 2 (A) To reduce the risk of pneumothorax, a longer approach is used to biopsy the subpleural lesion rather than the shortest one (dotted line). (B) To reduce the risk of pneumothorax and avoid ribs, a longer path is selected. (C) Oblique biopsy path chosen to avoid fissure (dotted line) and the rib. (D) Lesion biopsied in decubitus position to shorten the skin to the lesion's distance. The posterior approach was not suitable because of a fissure (dotted line), and the anterior entry was very long (arrow).

 

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Conflict of Interest

None declared.

Patient's Consent

Patient consent is not required.

• References

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Publikationsverlauf

Artikel online veröffentlicht:
04. Juni 2025