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1 Department of Radiology, Brigham and Women's Hospital and Harvard Medical
School, 75 Francis St., Boston, MA 02115.
2 Department of Pathology, Brigham and Women's Hospital and Harvard Medical
School, Boston, MA 02115.
3 Department of Radiology, University of North Carolina at Chapel Hill, 2016 Old
Clinic Building, Campus Box 7510, Chapel Hill, NC 27599-7510.
Received July 11, 2002;
accepted after revision October 16, 2002.
Address correspondence to F. J. Rybicki.
Abstract
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MATERIALS AND METHODS. We categorized 115 consecutive percutaneous biopsies of renal masses in 113 patients into four clinical settings and three groups of mass sizes. The sensitivity and negative predictive value were computed (with 95% confidence intervals [CI]) for each clinical setting and for each size group.
RESULTS. For all procedures (n = 115), the sensitivity and negative predictive value were 90% (95% CI, 81-95%) and 64% (95% CI, 44-81%), respectively. For patients with a known malignancy who presented with a renal mass (n = 55), the sensitivity and negative predictive value were 90% (95% CI, 78-96%) and 38% (95% CI, 10-74%), respectively. For patients with no known malignancy and suspected unresectable tumor (n = 36), the sensitivity and negative predictive value were 92% (95% CI, 76-98%) and 0%, respectively. For patients with no known malignancy who presented with a cystic mass (n = 16), the sensitivity and negative predictive value were 33% (95% CI, 2-87%) and 87% (95% CI, 58-98%), respectively. For patients who were not surgical candidates with a renal cell carcinoma (n = 8) that was thought to be resectable, both the sensitivity and negative predictive value were 100%. For masses 3 cm and less (n = 31), the sensitivity and negative predictive value were 84% (95% CI, 63-95%) and 60% (95% CI, 27-86%), respectively. For masses between 4 and 6 cm (n = 42), the sensitivity and negative predictive value were 97% (95% CI, 83-100%) and 89% (95% CI, 51-99%), respectively. For masses greater than 6 cm (n = 42), the sensitivity and negative predictive value were 87% (95% CI, 71-95%) and 44% (95% CI, 15-77%), respectively.
CONCLUSION. Percutaneous renal mass biopsy has a high sensitivity in
three clinical settings: patients with a known malignancy, patients with no
known malignancy and suspected unresectable tumor, and nonsurgical patients
with a mass suspected to be a resectable renal cell carcinoma. Negative
results in small (
3 cm) and large (> 6 cm) masses should be viewed
with caution.
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3 cm) masses have been
described [11,
12,
13], we believe that there has
been a paucity of data on biopsy performance as a function of clinical setting
and size groups of renal masses. Our study reviews 115 consecutive
percutaneous biopsies of renal masses performed at our institution and
evaluates the sensitivity and negative predictive value for all renal masses,
each clinical setting, and three groups of mass sizes. |
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Clinical Settings for Percutaneous Biopsies of Renal Masses
The first clinical setting consisted of patients with a known primary
malignancy (n = 55; extrarenal, n = 54; renal cell carcinoma
occurring after kidney-sparing surgery, n = 1) who presented with a
renal mass suspected to be a neoplasm. In these patients, a percutaneous renal
mass biopsy had been requested to differentiate a surgically resectable renal
cell carcinoma from a metastasis because virtually all metastases are treated
medically. The number of patients in this setting who presented with a cystic
mass suspected to be a malignancy was documented.
The second clinical setting (n = 36) consisted of patients with no known malignancy who presented with a renal mass that had imaging features suggesting that the mass was unresectable. In these patients, selection of the appropriate therapy was dependent on the biopsy results. This group included patients with suspected but undiagnosed metastatic disease (for example, a renal mass and a lung mass) as well as patients who presented with a renal mass that was directly invading an adjacent organ, a vascular structure, or both. For patients in whom multiple lesions were identified, the renal mass rather than an extrarenal lesion underwent biopsy because of the accessibility of the renal mass. All the patients in this group were treated medically, and the percutaneous renal mass biopsy was requested as a means of minimally invasive tissue diagnosis before medical treatment was initiated.
The third clinical setting for which percutaneous renal mass biopsy was requested included patients with no known malignancy who presented with a cystic renal mass that was indeterminate for malignancy (n = 16). Although we now rarely biopsy a complex cystic renal lesion, percutaneous biopsy of the solid portion of these masses was performed at the request of the referring clinician in an attempt to diagnose renal cell carcinoma.
The fourth clinical setting (n = 8) included patients who were not surgical candidates at the time of biopsy but who presented with a renal mass that had imaging features suggesting a resectable renal cell carcinoma. The role of percutaneous renal mass biopsy in this setting was to establish a tissue diagnosis before the initiation of an alternate therapy, such as chemotherapy or nephrectomy after treatment of reversible coexisting disease.
Procedures
Biopsies were guided using CT (n = 76), sonography (n =
28), both CT and sonography (n = 5), or MR imaging (n = 6).
In 92 of the 115 biopsies, only fine (20- or 22-gauge) needles were used in
tandem with an initially placed fine needle. In 23 biopsies, at least one
sample was obtained with a larger needle. Of these, the largest needle was 19
gauge in one patient, 18 gauge in 20 patients, 16 gauge in one patient, and 14
gauge in one patient. All biopsy needles that were 19 gauge and smaller were
end-cutting; needles that were 18 gauge and larger were side-cutting. Three to
five specimens were obtained from each mass. A cytopathology team was present
during all procedures to evaluate adequacy of the specimens. Three patients
developed a small, self-limited subcapsular hematoma. None required blood
products or hospital admission. Patients who developed a hematoma were
observed in the radiology department; CT follow-up in all patients confirmed
resolution or stability.
Data Collection
For each patient, radiology reports, an interventional radiology database,
a cytopathology database, and hospital medical records were reviewed to obtain
the size of the renal mass, the type of image guidance used for the
percutaneous renal mass biopsy, the results of imaging studies performed
before and after the biopsy, the cytological diagnosis, and clinical follow-up
data.
In all 115 patients, cytopathology reports were reviewed by a cytopathologist and then classified and categorized (Table 1). Results of the percutaneous renal mass biopsy were defined as positive if the cytopathologic examination revealed a renal cell carcinoma, a metastasis, or a specific extrarenal malignancy invading the kidney. In all other cases, the biopsy results were considered negative, including those specimens in which cytopathology revealed malignancy not otherwise specified (i.e., the malignant cells were found, but the type of tumor could not be specified).
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In the three cases in which malignancy was not otherwise specified, the results of percutaneous renal mass biopsy were considered negative despite the identification of a malignancy. This definition was adopted because malignancy was already strongly suspected on the basis of imaging and clinical criteria, and the goal of percutaneous renal mass biopsy was to subtype the malignancy for appropriate patient management. For example, if a cytologic distinction between a renal cell carcinoma and a sarcoma could not be made, the percutaneous renal mass biopsy result was defined as negative. Although both lesions require resection, the sarcoma requires wider surgical margins. Also, when a high-grade sarcoma is diagnosed at our institution, extensive intraoperative sampling of the surgical margin for radiographically occult low-grade sarcoma is performed.
All positive percutaneous renal mass biopsy results (i.e. identification of a specific malignancy) were considered true-positive (i.e., the false-positive rate was defined as zero). All patients in whom the results of percutaneous renal mass biopsy were defined as negative were followed up. For these patients, the final diagnosis was made at surgical pathology or, if surgery was not performed, with data from imaging and clinical follow-up of no less than 12 months. If either surgery or follow-up confirmed the negative results of the percutaneous renal mass biopsy, the biopsy results were defined as true-negative. If the final diagnosis and the diagnosis based on the results of the percutaneous renal mass biopsy were discordant, the results of the biopsy were defined as false-negative.
Data Analysis
The sensitivity and negative predictive value were calculated for all
masses, masses in each clinical setting, and three size groups of masses: 1-3
cm (masses
3.4 cm), 4-6 cm (masses = 3.5-5.4 cm), and larger than 6 cm
(masses
5.5 cm). The sensitivity and negative predictive value were also
calculated for biopsies in which only fine (20- or 22-gauge) needles were used
and those in which at least one sample was obtained using a larger gauge
(19-gauge or larger) needle. Comparison between groups was performed using 95%
confidence intervals (CI).
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Clinical Settings
Patients with a known extrarenal primary cancer and a renal mass
suspected to be malignant.The sensitivity and negative predictive
value were 90% and 38%, respectively (Table
2). Three of the five patients in whom the biopsy results were
false-negative had a renal mass that was 3 cm or smaller
(Table 3). In the 54 patients
with a known extrarenal primary cancer, 31 masses (57%) proved to be renal
cell carcinoma rather than metastases
(Table 4). Six of the 54
patients with a known extrarenal primary cancer presented with a cystic renal
mass that was highly suspicious for malignancy; the remaining masses were
solid. None of the six cystic masses were metastases.
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Patients with no known malignancy but whose imaging findings suggested an unresectable tumor.In 36 patients with a renal mass in the setting of unresectable tumor, percutaneous renal mass biopsy identified the cell type of the malignancy in all but three cases (Table 2). In each of the three patients with false-negative results (Table 3), the renal mass was large (> 6 cm), and the malignant cells were found at cytopathology; however, the type of tumor could not be specified (malignancy not otherwise specified). In two of the patients, the distinction between sarcoma and renal cell carcinoma could not be made, even with immunocytochemical studies. At surgery, masses in both patients were found to be renal cell carcinoma. The third patient in this group presented with both a renal mass and a pulmonary mass. Cytopathologic findings at percutaneous renal mass biopsy could not distinguish renal cell carcinoma from metastatic lung cancer. At surgery, the renal mass proved to be renal cell carcinoma. The pulmonary mass was subsequently biopsied and found to be adenocarcinoma of the lung.
Patients with a cystic renal mass that was indeterminate for malignancy.Of the 16 patients who underwent biopsy of a cystic renal mass (Table 2), two patients had false-negative biopsy results (i.e., the biopsy failed to reveal the renal cell carcinoma that was found at surgery). Of the 13 patients with true-negative results, two had the biopsy results confirmed at nephrectomy, and 11 had the biopsy results confirmed by follow-up data that showed neither growth of nor morphologic change in the mass. Both the mean and median lengths of imaging follow-up were 26 months, with a range of 12-49 months. The lengths of mean and median clinical follow-up were 38 and 35 months, respectively, with a range of 12-65 months.
Patients who were not surgical candidates with a mass suspected to be resectable renal cell carcinoma.Of the eight patients in this group, two had a true-negative result (Table 2). In both cases, the cytopathologic findings were negative, and the patients were followed up with imaging (mean length of follow-up, 26 months) and clinical (mean length of follow-up, 40 months) examinations.
Mass size
The sensitivity and negative predictive value for the 115 percutaneous
renal mass biopsy cases were evaluated with respect to mass size
(Fig. 1). Although the highest
sensitivity and highest negative predictive value were found in masses
measuring 4-6 cm (Table 5), no
statistical difference among the three size groups was found at the 95%
confidence level.
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Biopsy Needle Size
Biopsies that included at least one specimen obtained with a larger needle
yielded a higher sensitivity and higher negative predictive value
(Table 6). In fact, in all 10
percutaneous renal mass biopsies with false-negative results, only fine (20-
or 22-gauge) needles were used. However, no statistical difference in biopsy
performance between fine and large needles was found at the 95% confidence
interval.
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Percutaneous biopsy of a renal mass was requested in four major clinical
settings. The high sensitivity (90%) of the biopsy results in patients with a
known primary cancer strongly supports the use of percutaneous renal mass
biopsy to identify those patients with renal cell carcinoma who need surgery.
Although five of the 55 patients in this group had false-negative biopsy
results (three patients with false-negative results had masses that were
3 cm), alternative management strategies for such patients have significant
drawbacks. Surgery carries significant risk of morbidity and is usually not
indicated for a metastatic lesion. Short-term imaging follow-up without
intervention, even for small masses, is not prudent because only three masses
in patients in this clinical setting proved to be benign. However, because of
the low negative predictive value of biopsy results in this group, we
recommend surgery if biopsy fails to reveal a neoplasm, especially in the case
of a small mass for which partial nephrectomy is an option.
The evaluation of the results of a percutaneous renal mass biopsy in 54 patients with a known extrarenal primary cancer who presented with a new renal mass offered two additional conclusions. First, none of the suspicious cystic renal masses proved to be a metastatic lesion, suggesting that a cystic renal mass is rarely a metastasis. Consequently, we now recommend considering surgery without a percutaneous renal mass biopsy in patients with an extrarenal cancer who present with a highly suspicious cystic renal mass. Second, the two most common primary cancers for which percutaneous renal mass biopsies were performed were lymphoma (n = 20) and lung cancer (n = 16). Despite the metastatic potential of these tumors, a new renal mass proved to be renal cell carcinoma in half the cases. This result, combined with the inability to use imaging features to differentiate between a metastasis and a renal cell carcinoma, emphasizes the need to biopsy a renal mass that has no benign characteristics (such as the identification of fat in an angiomyolipoma) in patients with lymphoma and patients with lung cancer rather than to assume the mass is a metastasis (Figs. 2A, 2B and 2C).
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The next most common clinical setting for percutaneous renal mass biopsy was a patient with no known primary malignancy who presented with imaging findings that suggested that curative surgery was not possible. In these patients, the biopsy of a renal mass could potentially result in less morbidity than the biopsy of an extrarenal lesion. For example, a pneumothorax could be avoided in a patient presenting with both a lung mass and a renal mass if the percutaneous renal mass biopsy revealed metastatic lung cancer. However, if percutaneous renal mass biopsy yielded renal cell carcinoma, the lung mass would still require biopsy if one wanted to differentiate metastatic renal cell carcinoma from primary lung cancer. The sensitivity of percutaneous biopsy supports its use in establishing a diagnosis in this group of patients.
In all three patients with false-negative results in this group, the renal mass was larger than 6 cm, a fact that raises the possibility of a sampling error. The risk of sampling error is greater in large masses that are more likely to contain necrosis [30]. In general, an attempt is made to avoid sampling necrotic areas; however, imaging is not always an accurate indicator of necrosis.
The second factor that influenced the test characteristics was the patient management-based definition of a false-negative result. As previously discussed, the cases in which sarcomatoid renal cell carcinoma could not be distinguished from sarcoma were judged as a false-negative result. For example, if the definition were broadened so that a procedure with a cytopathologic finding of malignancy not otherwise specified were considered true-positive, all 36 patients in this group would have been found to have true-positive results.
With this definition, the overall sensitivity and negative predictive value of the 115 biopsies would have been 93% (95% CI, 85-97%) and 72% (95% CI, 50-87%), respectively. If the broader definition were applied to masses larger than 6 cm, calculations would have rendered a sensitivity of 95% (95% CI, 81-99%) and a negative predictive value of 67% (95% CI, 24-94%). The difficulty in distinguishing sarcoma from sarcomatoid renal cell carcinoma is due largely to the imperfect sensitivity of immunocytochemistry for keratin proteins [31]. More sensitive markers for epithelial, or more specifically renal epithelial, differentiation would inevitably improve the sensitivity and negative predictive value of percutaneous renal mass biopsy in large renal masses.
The most controversial of the clinical settings for which we were asked to perform percutaneous renal mass biopsy was the cystic renal mass [32, 33]. There are three principal treatment options for managing a cystic renal mass: observation, percutaneous renal mass biopsy, or surgery. In our experience, the percutaneous renal mass biopsy is the least commonly used, as evidenced by the fact that we performed biopsies of only 16 such masses in more than 10 years. Because our preference was to recommend surgery for suspicious masses, most masses that we biopsied were benign (Table 2). The sensitivity of percutaneous renal mass biopsy results in the diagnosis of cystic renal cell carcinoma is low, and therefore, a negative result at cytopathology is often not definitive enough to avoid performing surgery [34]. If surgery is not performed, follow-up is still required, and our experience with the two patients who had false-negative results emphasizes the limitation of a percutaneous biopsy in this clinical setting.
The analysis of percutaneous renal mass biopsy results stratified by mass size (Table 5 and Fig. 1) showed excellent results for masses measuring 4-6 cm. Although the series lacked the power to show a statistical significance among the three size groups, the lower negative predictive value in masses 3 cm or smaller (60%) was likely caused by technical factors related to the biopsy of a small mass and challenges the significance of a negative result in patients with a mass of this size.
As previously discussed, the low sensitivity among masses greater than 6 cm may be due to sampling error, and the 44% negative predictive value for these masses emphasizes the fact that almost all large solid masses selected for biopsy are malignant.
Our analysis of the effect of needle gauge on biopsy results showed that no false-negative biopsy results occurred in procedures in which a needle larger than 20 gauge was used (Table 6). However, large needles were used in only a small percentage of procedures, and no statistically significant difference between the fine and the large needles was found when sensitivity and negative predictive value were analyzed. Therefore, it is difficult to draw any specific conclusions regarding the benefit of large needles. Our data suggested that in most cases, renal cell carcinoma and other causes of renal masses can be diagnosed using fine needles alone. Although there may be a benefit to using large needles, these benefits must be weighed against the increased risk of bleeding and pseudoaneurysm formation [13, 35]. Overall, we recommend using fine needles for percutaneous renal mass biopsy and reserving the use of larger needles for selected cases.
Our study is limited in that surgical biopsy or resection (or both) was not possible in most patients who had negative biopsy results; we relied on imaging and clinical follow-up data for proof. Because renal cell carcinoma may be an indolent disease, there is no definite time period after which malignancy can be excluded. However, a minimum follow-up of 1 year was chosen as an alternative to surgical confirmation; the mean follow-up period in these patients was longer than 3 years.
In conclusion, our study reviewed 115 cases (113 patients) in which percutaneous biopsy was used in the evaluation of a renal mass. High sensitivity was found in patients with three clinical settings: patients with a known primary cancer for whom percutaneous renal mass biopsy was used to differentiate a surgically resectable renal cell carcinoma from a metastatic deposit, patients with no known malignancy whose imaging findings suggested an unresectable renal mass and for whom percutaneous renal mass biopsy was used for minimally invasive tissue diagnosis, and patients who were not surgical candidates whose imaging findings suggested a resectable renal cell carcinoma and for whom percutaneous renal mass biopsy was used for tissue diagnosis before the initiation of an alternative therapy. Renal cell carcinoma was found in half of our patients who had a new renal mass and either lung cancer or lymphoma; however, biopsy of such masses should be performed before therapy is instituted. Negative biopsy results in patients with renal masses 3 cm or smaller and larger than 6 cm should be viewed with caution. We recommend targeting small masses carefully and sampling large masses in several locations.
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