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Interventional Radiology |
1 Department of Radiology, Division of Abdominal Imaging and Intervention,
Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115.
2 Department of Radiology, Brigham and Women's Hospital and Dana Farber Cancer
Institute, 44 Binney St., Boston, MA 02115.
3 Present address: Department of Radiology, University of Massachusetts, 5 Lake
Ave., Worcester, MA.
4 Department of Pathology, Division of Cytology, Brigham and Women's Hospital,
Boston, MA 02115.
Received November 18, 2003; accepted after revision February 16, 2004.
Address correspondence to K. Tuncali
(ktuncali{at}partners.org).
OBJECTIVE. Percutaneous ablation of renal cell carcinoma has the potential to be as effective as partial nephrectomy. Because the entire tumor cannot be examined at pathology, diagnosis relies solely on imaging and percutaneous biopsy. Diagnoses of cancer have been rendered using imaging alone in some clinical trials of percutaneous ablation. If these trials inadvertently included benign masses, the efficacy of ablation was overestimated. Therefore, we sought to determine the prevalence of benign masses in a population of patients referred for percutaneous tumor ablation of presumed renal cell carcinoma.
SUBJECTS AND METHODS. Twenty-seven patients were referred by urologists for MRI-guided cryotherapy of suspected renal cell carcinoma. Renal masses ranged from 1.0 to 4.6 cm (mean, 2.2 cm) in diameter. The CT, MRI, and percutaneous biopsy findings were tabulated and compared with surgical and imaging follow-up.
RESULTS. Ten patients (37%) had a benign renal mass, including three angiomyolipomas, that had no evidence of fat on CT or MRI. Three masses were proven benign by biopsy, three by imaging, and four by a combination of biopsy and imaging. The masses in the remaining 17 patients were ablated. Biopsy revealed malignant cells in 10, suspicious cells in four, and atypical cells in two; one was nondiagnostic.
CONCLUSION. A substantial percentage of patients referred for percutaneous ablation of renal tumors had benign masses. If CT or MRI alone cannot be used to diagnose a benign entity, patients should undergo a biopsy before the treatment session.
After prostate and bladder carcinoma, renal cell carcinoma is the third
most common malignancy of the genitourinary tract, causing approximately
11,000 deaths per year in the United States
[1]. With the increasingly
common use of cross-sectional imaging, the discovery of incidental small (
3 cm) renal masses has become more frequent
[2–4].
The detection of incidental small renal masses poses diagnostic and
therapeutic dilemmas, such as distinguishing benign from malignant lesions and
deciding how to treat them. Radical nephrectomy has been the mainstay of
surgical treatment for patients with renal cell carcinoma
[5]; however, 5-year survival
rates for those with stage I tumors after partial nephrectomy are comparable
to those achieved with radical nephrectomy
[6–9].
Percutaneous tumor ablation techniques such as cryotherapy [10–12], radiofrequency ablation [13–18], and, more recently, extracorporeal techniques such as high-intensity focused ultrasound ablation [19] have been suggested as alternatives to partial nephrectomy for the treatment of patients with small renal cell carcinoma. These techniques have the potential to be as effective as partial nephrectomy and were associated with lower patient morbidity and faster convalescence. However, compared with surgical resection in which the entire tumor is examined at pathology, percutaneous and extracorporeal techniques rely solely on imaging and percutaneous biopsy for diagnosis. Several published trials of percutaneous tumor ablation of renal cell carcinoma have included patients who were treated with a presumptive diagnosis of renal cancer on the basis of imaging features alone without undergoing a percutaneous biopsy [11–14, 17, 18]. As a result, treatment efficacy may have been overestimated if benign lesions were included in their data.
Without a preprocedural percutaneous biopsy, a tissue diagnosis is not obtained and patients with benign lesions may be treated unnecessarily. Therefore, we retrospectively evaluated patients with presumed renal cell carcinoma referred by urologists to our clinical trial of percutaneous tumor ablation of renal tumors to determine the prevalence of benign lesions and to better define the roles of imaging and percutaneous biopsy before ablation of renal masses.
Subjects and Methods
Subjects
Twenty-seven patients referred to us by urologists for enrollment in a
clinical trial approved by the institutional review board evaluating
percutaneous MRI-guided cryotherapy of renal tumors were considered eligible
for treatment and formed the basis of this study. Written informed consent was
obtained from all patients who underwent cryotherapy and percutaneous biopsy.
The mean age of the study group was 66 years (range, 43–86 years); there
were 11 women and 16 men. All patients had a CT examination, an MRI
examination, or both that revealed a renal mass that was interpreted as
suspicious for renal cell carcinoma on the basis of the presence of contrast
enhancement of all or a portion of the mass, leading to the referral of the
patient to the urologist. There were 29 renal masses in 27 patients; two
patients had two masses each. Renal mass diameters ranged from 1.0 to 4.6 cm
(mean, 2.2 cm). Of the 29 masses, 25 (86%) were less than or equal to 3
cm.
Preprocedural Assessment
All patients were examined on either CT (n = 3) or MRI (n
= 9) or both (n = 15). CT scans were obtained using 5-mm collimation
through the kidneys before and after IV administration of 100 mL of iopromide
300 mg I/mL (Ultravist 300, Berlex Laboratories). If not already performed
before referral, an MRI examination was performed to serve as the baseline
study to which postablation MRI examinations could be compared and to assist
in the planning of the MRI-guided treatment. The 1.5-T MRI protocol was
limited to the abdomen and included axial T2-weighted imaging (slice
thickness, 4–5 mm; gap, 1 mm; field of view, 36–40 cm) either
using a fast spin-echo sequence (TR/TE, 5,817/100; echo-train length, 12;
number of slices, 36) or using a breath-hold fast-recovery fast spin-echo
sequence (1,850/90; echo-train length, 19; number of slices, 38) and a
single-shot fast spin-echo sequence (TE, 370 msec; number of slices, 40).
Axial T1-weighted imaging (gap, 1 mm; field of view, 40 cm) using a spin-echo
sequence (TR range/TE, 500–600/14; slice thickness, 4–5 mm; number
of slices, 36; respiratory compensation, on) or using a breath-hold spoiled
gradient-recalled acquisition in the steady state (GRASS) sequence
(TR/first-echo TE, second-echo TE, 400/2.2, 4.6; flip angle, 90°; slice
thickness, 5 mm; number of slices, 40) was performed. Axial fat-suppressed
T1-weighted dynamic gradient-echo imaging with breath-hold spoiled GRASS (TR
range/TE, 300–450/4.2; flip angle, 75°; slice thickness, 4–5
mm; gap, 1 mm; field of view, 40 cm; number of slices, 40) was also performed
before and four phases after the IV administration of 20 mL of gadopentetate
dimeglumine 469.01 mg/mL (Magnevist, Berlex Laboratories).
The preablation evaluation by the interventional radiology staff included a
disease-focused history and careful evaluation of all CT scans and MR images,
including a thorough search for the presence or absence of fat and enhancement
within the renal mass. Fat was identified using CT if a region of interest
(
3 pixels) contained an attenuation less than or equal to –10 H.
Fat was identified using MRI if a mass contained a focus of increased T1
signal that showed signal intensity loss on fat-suppressed T1-weighted images.
On CT scans, enhancement within a renal mass was considered unequivocal when
the mean attenuation of a centrally placed region of interest increased at
least 20 H. On MRI, enhancement was considered unequivocal when a portion of
the mass enhanced by 20% or more (signal intensity change divided by native
signal intensity), using a similarly placed region of interest
[20]. On CT scans, enhancement
was considered equivocal when the increase was 10–19 H or when the only
enhancing focus in the mass was smaller than 5 mm. On MRI, enhancement was
considered equivocal when the percentage of enhancement was 15–19%.
Biopsy Procedures
Twenty-six percutaneous needle biopsies were performed in 24 of the 27
patients. In nine of these patients, only MRI-guided (0.5-T open
configuration) biopsy was performed during the cryotherapy procedure, just
before the treatment. These patients presented early in the study. Later, 13
patients underwent only a CT-guided biopsy before the day of the planned
ablation. Two patients had biopsies both before the day of the ablation and
during the ablation session just before treatment. One patient who had a
history of familial multifocal renal cell carcinoma had two adjacent lesions
of similar appearance; only one was biopsied.
All percutaneous biopsies were performed using fine needles (22-gauge, 20-gauge, or both; Chiba needle, Cook; or Lufkin MRI-compatible biopsy needle, E-Z-EM) except in one case in which only an 18-gauge needle (Lufkin MRI-compatible biopsy needle) was used. The number of needle samples for each mass ranged from two to seven (mean, 4.4). A cytologist was present during the biopsy procedure for immediate assessment for adequacy of the specimen. Preliminary cytopathology results were available the day of the procedure, and final cytopathology results typically were reported 2–5 days later. Cytologic results were reported as no malignant cells identified, atypical cells present, suspicious cells present, positive for malignant cells, or nondiagnostic (acellular specimen or visualized cells obscured by blood, inflammation, or artifact). Whenever possible, a specific cytopathologic diagnosis was rendered (e.g., angiomyolipoma, renal cell carcinoma).
Analysis
Patient age and sex, mass size, CT and MRI findings, biopsy results, and
complications were tabulated. The percentage of benign lesions was determined.
The presence of fat in a renal mass in the absence of calcification was
considered diagnostic of angiomyolipoma
[21]. Although fat-containing
renal cell carcinomas have been reported, they are rare, found only in
sporadic case reports, and are almost always in masses containing
calcifications [22]. Biopsy
results were considered benign if a specific benign diagnosis (e.g.,
angiomyolipoma) was rendered in the pathology report or if the biopsy specimen
revealed no malignant cells or was nondiagnostic and the mass was stable on
follow-up imaging for at least 1 year. Biopsy results were considered positive
for malignancy if biopsy specimens contained malignant cells. The remainder
were classified separately as suspicious cells present, atypical cells
present, or nondiagnostic.
Results
Of 27 patients referred for percutaneous tumor ablation of suspected renal cell carcinoma and considered for treatment, 10 (37%) had a benign renal mass (Table 1). All benign masses were 2 cm or smaller. Three had a specific benign diagnosis at biopsy (Figs. 1A, 1B, 1C and 2A, 2B, 2C), including one that was treated. In the latter case, an angiomyolipoma was inadvertently treated because the biopsy was performed during the treatment session and the result was not available until several days later. Three masses were diagnosed as benign by imaging or by regression of the mass on follow-up imaging (Figs. 3A, 3B, 3C and 4A, 4B, 4C). Four patients had masses that showed no change (mean follow-up, 15.3 months; range, 12–18 months). Each of these latter four masses had exhibited only equivocal enhancement; at biopsy, three showed no malignant cells and one was nondiagnostic.
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The remaining 17 patients were treated with percutaneous MRI-guided cryotherapy. At presentation, all but one mass were solid and exhibited homogeneous enhancement. A 1.3-cm mass was cystic and contained a small internal nodule that enhanced equivocally. These patients underwent 19 percutaneous biopsy procedures. In two patients, renal masses were biopsied twice: once before the day of the ablation and then during the ablation session. In one patient, atypical cells were obtained after the first biopsy was nondiagnostic. In the other patient, malignant cells were obtained after the first biopsy revealed only suspicious cells. The final biopsy result revealed malignant cells in 10, suspicious cells in four, and atypical cells in two; one was nondiagnostic. Of the 10 biopsies with malignant cells, a specific diagnosis was rendered in all (nine renal cell carcinomas, one transitional cell carcinoma) (Figs. 5A and 5B). In all four biopsies with suspicious cells, the cells were reported to be suspicious for renal cell carcinoma. A diagnosis of the papillary subtype of renal cell carcinoma was rendered in six patients; the remainder could not be subclassified.
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Of the nine patients in whom biopsy was performed during the ablation session only, the biopsy result revealed angiomyolipoma in one, malignant cells in four, suspicious cells in two, atypical cells in one, and was nondiagnostic in one. In the latter case, the diagnosis of renal cell carcinoma was made at partial nephrectomy performed for a recurrence detected 6 months after ablation. As a result of these cases, including the case in which an angiomyolipoma was inadvertently treated, we biopsied masses in advance of ablation in 15 patients, nine of whom were later treated. This preprocedural biopsy provided definitive diagnosis of renal cell carcinoma in five patients. There were two patients whose biopsies revealed cells suspicious for renal cell carcinoma who were later treated with ablation. Another two patients, one with suspicious cells and the other with a nondiagnostic result, were also treated; the repeated biopsy performed during the ablation session revealed renal cell carcinoma in one and atypical cells in the other. The decision to proceed with ablation in these four patients after their initial nondefinitive biopsy was based on the high likelihood that the masses were malignant according to imaging findings and the wishes of both the patient and their referring physician.
Discussion
Nephron-sparing surgical treatments for renal cell carcinoma, such as enucleation or partial nephrectomy, have historically been reserved for patients with bilateral tumors, solitary kidneys, and renal insufficiency [23, 24]. However, 5-year survival rates for patients who undergo nephron-sparing treatment are similar to those of patients who undergo radical nephrectomy [8, 9]; as a result, indications for nephron-sparing treatment have expanded to include the treatment of cancers that are small, unilateral, or detected in patients with von Hippel-Lindau disease [24, 25]. Although data are preliminary, percutaneous ablation could replace surgical extirpation for the treatment of renal cell carcinoma [10–18, 24]. Unlike surgical treatments in which renal mass diagnosis is based on a pathologist's analysis of the entire resected specimen, diagnosis relies solely on imaging or a pretreatment percutaneous biopsy when masses are treated with percutaneous ablation. Of published reports on percutaneous renal tumor ablation, diagnoses of cancer have been rendered by biopsy in only two [15, 16], by imaging alone in three [11, 12, 14], and by biopsy or imaging in three [13, 17, 18]. In one trial, the diagnostic method was not described [10]. If these clinical trial results included benign masses, the efficacy of ablation in the treatment of renal cancer was overestimated. Furthermore, in clinical practice, without a tissue diagnosis, benign lesions may be treated unnecessarily and patients subjected to unnecessary invasive procedures with potential complications and follow-up care and cost.
In our series, 37% of patients referred for ablation of presumed renal cell
carcinoma harbored a benign mass. The inadvertent treatment of a benign renal
mass can be avoided through careful preprocedural imaging analysis and routine
biopsy of all masses that cannot be diagnosed as benign on imaging alone. The
conventional approach for characterizing renal masses is by cross-sectional
imaging, including CT before and after the administration of IV contrast
material; sonography and MRI are often supplemental
[21,
26,
27]. Simple cysts,
pseudotumors (e.g., columns of Bertin), inflammatory masses (e.g., focal
bacterial pyelonephritis), and angiomyolipomas are benign entities that
typically are diagnosed with imaging and clinical findings alone
[21,
26,
27]. Lymphoma and metastases
are other examples of masses that may not require ablation, should be
suspected with an appropriate history, and can be proven by percutaneous
biopsy [21,
26,
27]. After these entities are
excluded, an enhancing renal mass in an adult is usually renal cell carcinoma.
However, not all enhancing masses are malignant. For example, 10% of small
( 3 cm) masses are estimated to be oncocytoma
[21], which, in general, is
considered a benign entity
[28].
Our series shows the important role of the interventional radiologist and cytopathologist in the preprocedural diagnosis of renal masses—that is, the importance of carefully evaluating preprocedural imaging, obtaining a clinical history, and performing a preprocedural biopsy in all cases that cannot be diagnosed with certainty by imaging alone. Only after being referred for ablation was the presence of subtle fat detected in a renal mass in a patient with an angiomyolipoma. Focal bacterial pyelonephritis was recognized by combining imaging findings with a recent history of a urinary tract infection. The diagnosis was established by proving regression of the mass at follow-up imaging while the patient was taking antibiotics. Another patient's preablation evaluation was delayed because of comorbidity; in the interim, regression of the mass at follow-up imaging established a benign diagnosis.
The conventional notion regarding percutaneous biopsy for the characterization of small renal masses is that it has a limited role [21]. Historically, biopsy has been reserved for specific clinical settings in which it has been shown to be useful, such as differentiating renal cell carcinoma from lymphoma, metastasis, and abscess [21]; diagnosing unresectable renal cancers; and diagnosing the cause of a renal mass in a patient who is not a surgical candidate [29]. Indeed, biopsy has been shown to be effective and safe in diagnosing renal cell carcinoma in these clinical settings [30]. Serious complications such as needle tract seeding may occur, but these complications are rare [31]. Our study shows an additional important role of percutaneous biopsy in patients referred for percutaneous tumor ablation of suspected renal cell carcinoma. Imaging cannot be used alone to distinguish renal cell carcinoma from an angiomyolipoma with minimal or no fat or a rare benign mesenchymal renal tumor such as a fibroma or leiomyoma [21]. Approximately 5% of angiomyolipomas contain no visible fat on CT or MRI and are indistinguishable from small renal cell carcinoma on imaging [32, 33]. We had three such cases proven by biopsy.
One angiomyolipoma was inadvertently treated because the biopsy was performed during the treatment session and the result was not available until several days later. Although treatment was not avoided, performing the biopsy did prevent unnecessary follow-up that would have otherwise been undertaken if the biopsy had not been performed. As this case illustrates, a percutaneous biopsy should be performed as a separate procedure before the day of the ablation to allow sufficient time for a tissue diagnosis to be established before under-taking any treatment.
Characterization of incidentally discovered, small, and, particularly, very
small ( 1.5 cm) renal masses by imaging alone has limitations
[21,
34]. Enhancement may be
equivocal (10–19 H) in small masses. Despite the use of thin sections,
partial volume averaging may lead to either missing or falsely identifying
enhancement. In six of our patients, enhancement was equivocal; all were less
than or equal to 2 cm, and three were cystic. One lesion was diagnosed as
benign on the basis of regression on imaging. However, percutaneous biopsy was
helpful in the management of the other five cases. In one patient, cells
suspicious for renal cell carcinoma were found at biopsy and the mass was
treated. In the other four patients, the biopsy revealed no malignant cells
and all have been stable for at least a year. Although there is no known
interval of time that can be used to exclude renal cell carcinoma, lack of
change in 1 year is sufficient to conclude that these masses were almost
certainly either histologically benign or low-grade renal cell carcinoma.
Because most small renal carcinomas grow slowly and are unlikely to
metastasize [35], a
conservative approach to following these masses with imaging has been
proposed. This approach may be particularly appropriate for masses smaller
than 2 cm, in the elderly, or in patients with comorbid illness
[21]. Five of 27 patients in
our series were 80 years old or older. Hence, the risks of percutaneous tumor
ablation, although likely lower than surgical resection, may be greater than
the risk of observation. Although an argument could be made for not ablating
masses in patients in this age group, a stronger one could be made to obtain a
tissue diagnosis first before treating them.
In addition to using imaging and biopsy to prevent benign masses from being
ablated, obtaining a tissue diagnosis of malignancy before ablation is also
important. We were able to achieve this in 10 of the 17 patients we believed
to have malignant masses. Percutaneous renal mass biopsy has been shown to be
accurate in the general population with renal masses
[29]. However, it is more
limited in small ( 3 cm) masses
[29] and, at times, results
may not be definitive. Indeed, we treated four patients whose biopsies
revealed cells suspicious for renal cell carcinoma, two whose biopsies
revealed atypical cells, and one whose biopsy was nondiagnostic. All seven of
these patients had small masses. In five of these patients, biopsies were all
obtained during the ablation session and the results were not available until
several days later. The ablation was performed, according to protocol, on the
presumption that the masses were malignant. As a result of this study, we now
advocate biopsy before the day of the ablation. If the biopsy reveals a benign
result, ablation can be avoided. If the biopsy yields a malignant result,
ablation can be performed. If the preprocedural biopsy reveals suspicious or
atypical cells, ablation could be performed because it has been shown that, in
general, abdominal masses that contain suspicious or atypical cells are often
malignant [36]. Alternatively,
the biopsy could be repeated or the mass could be followed. From the
standpoint of clinical practice, these decisions can be made on the basis of
the likelihood the mass is malignant by imaging and the individual wishes of
the patient and referring physician. From the point of view of a clinical
trial evaluating the efficacy of ablation, these masses should be noted and
perhaps analyzed separately.
The results of our study are preliminary because our series represents a small number of patients. However, the high percentage of benign masses encountered in our series is important to convey to prevent patients from undergoing ablation unnecessarily. Furthermore, these data may help encourage other researchers to report ablation results only in biopsy-proven disease so results of series can be accurately compared. Another limitation of our study is that we biopsied renal masses with fine needles (20- and 22-gauge) almost exclusively. If we had used needles larger than 20-gauge, the sensitivity and negative predictive value of the procedure may have increased [29]. The benefit of using large needles, to our knowledge, has not been proven in a statistically valid comparison study. Also, because an ablated tumor cannot be fully evaluated as completely as a surgically resected one, the only way to subclassify and grade the tumor is with biopsy. Indeed, subclassification and grading of renal cell carcinomas have important prognostic implications [37]. In our series, subclassification was possible with biopsy in six patients. The use of large needles (e.g., 18-gauge or larger) may improve our ability to subclassify and perhaps grade renal cell carcinoma [30].
In conclusion, in our experience, a substantial percentage of patients referred for percutaneous ablation of renal tumors had benign masses. As a result, we recommend that patients with renal masses referred for ablation be examined first with CT or MRI. If imaging alone cannot prove benignity, patients should undergo a preprocedural percutaneous biopsy before the treatment session and be treated with ablation if the biopsy sample is positive for malignancy. If the preprocedural biopsy yields suspicious or atypical cells or is nondiagnostic, the decision of whether to proceed with ablation should be made in consultation with the referring physician, the pathologist, and the patient.
References
3.0 cm) renal parenchymal tumor:
detection, diagnosis, and controversies. Radiology1991; 179:307
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