Bosniak Category IIF and III Cystic Renal Lesions: Outcomes and Associations

Introduction

The Bosniak renal cyst classification system, first described in 1986 (1), is a well-established, widely used method that uses computed tomographic (CT) findings to categorize cystic renal masses into groups on the basis of imaging features associated with malignancy. In brief, Bosniak category I and Bosniak category II cystic renal lesions are simple and mildly complex cysts, respectively, and require no further evaluation. Bosniak category IV cystic renal lesions are almost certainly malignant and are resected in clinically able patients. Bosniak category III cystic renal lesions are indeterminate in malignant potential and most commonly managed with surgical excision. While the malignancy risk of Bosniak III cystic lesions is thought to be approximately 50% (2), reported malignancy rates range from 31% (3) to 100% (4). Furthermore, studies published to date have included relatively small numbers of lesions: Four studies described fewer than 15 Bosniak III lesions each (3–6), one included 33 (7), and the largest included 49 (8). Bosniak category IIF is a modification of the initial classification used to describe a group of cystic lesions that are more complex than Bosniak II lesions but not complex enough to be characterized as Bosniak III lesions. Bosniak category IIF cystic renal lesions generally undergo imaging surveillance to demonstrate stability over the course of time, a feature associated with benignity (9). There have been several studies evaluating surveillance of Bosniak IIF lesions (7,9), but because they are believed to be benign, there are few studies that have evaluated resected Bosniak IIF lesions (10).

We performed a retrospective review of Bosniak IIF and Bosniak III lesions to evaluate the clinical outcomes, pathologic diagnoses, metastatic disease rate, and clinical features associated with malignancy.

Materials and Methods

Identification of Patients with Bosniak IIF and III Cystic Renal Lesions

Informed consent was waived in this institutional review board–approved, Health Insurance Portability and Accountability Act–compliant retrospective study. A database with integrated data from our radiology (Syngo Workflow; Siemens Medical USA, Malvern, Pa) and hospital (Epic Systems, Verona, Wis) information systems was searched for the term “Bosniak” combined with “IIF” or “2F” or “III” or “3” from January 1, 1994 to August 31, 2009 in reports from CT or magnetic resonance (MR) imaging studies performed in patients 18 years or older. The search of approximately 100 000 reports yielded 3215 examinations. Inclusion criteria for the study group were unenhanced and contrast material–enhanced CT examination results and surgical resection of the lesion or 1 year or more of imaging follow-up of the lesion. Patients with Bosniak IIF or Bosniak III lesions in which biopsy and ablation were percutaneously performed and those lesions that were not resected but had less than 1 year of imaging follow-up were excluded from analysis. Patients with von Hippel-Lindau syndrome were excluded from analysis because the great majority of cystic renal neoplasms in these patients are malignant clear cell renal cell carcinoma (RCC).

A total of 308 patients with Bosniak IIF and/or Bosniak III lesions were identified. Of these, 113 patients were excluded from analysis because of lack of surgical excision with less than 1 year of imaging follow-up. Seven of these patients with eight Bosniak III lesions had benign pathologic findings at percutaneous biopsy (seven core-needle biopsies and one fine-needle aspiration biopsy) and were excluded because of potential sampling error. An additional two patients were excluded because of unclear surgical pathologic findings (n = 1) or a history of von Hippel-Lindau syndrome (n = 1). A total of 69 Bosniak IIF lesions in 62 patients and 144 Bosniak III lesions in 131 patients were included in the final analysis.

A CT study both without contrast material and with intravenous contrast material was used for initial classification with the Bosniak grading system in 92% (178 of 193) of patients, and MR imaging without and with intravenous contrast material was used in 8% (15 of 193) of patients for the initial classification. If MR imaging was the first examination performed, CT performed later in the patient’s clinical course was utilized for lesion characterization in this study.

Data Collection and Surgical Pathologic Correlation and Follow-up

Clinical data recorded from the electronic medical record included patient sex; date of birth; age at initial application of Bosniak classification; date of initial imaging examination used for Bosniak classification; specialty of the physician who ordered the imaging study used to classify the lesion (urologist or nonurologist); history of hemodialysis; history of malignancy (primary renal tumor or neoplasm originating in another organ) or Bosniak IV lesion; date of the last clinical note; and, when present, the date of development of metastatic disease from a primary renal malignancy. The imaging reports from the time of initial application of the Bosniak criteria until the last available imaging report were assessed for each patient, and the date of any reclassification of a Bosniak category was recorded. All Bosniak IIF lesions that were later categorized as Bosniak III lesions were categorized as Bosniak III lesions in the pathologic and clinical analysis. Because a number of Bosniak IIF and III lesions were reclassified at follow-up imaging, a radiologist with 17 years of experience (E.M.R.) reevaluated the images to determine whether reclassification resulted from a change in the lesion imaging characteristics or, if no change, from differing opinions of the original interpreting radiologists.

In addition, the practice type of the radiologist who initially classified the lesion (fellowship-trained academic or community-based radiologist), the number and side (right and/or left kidney) of the Bosniak IIF or III lesions, the number and side of coexisting Bosniak IV lesions and/or solid renal mass, and the type of imaging studies used to initially classify the Bosniak cystic lesions were recorded.

All imaging studies were reviewed to identify the axial section thickness and to determine if multiplanar reformations were obtained and archived. For patients with surgical resection of Bosniak IIF and/or Bosniak III lesions, the date of surgery was recorded, and the interval from initial Bosniak classification to surgery was calculated. The pathology specimen reports from these patients were reviewed, and the lesions were classified as benign or malignant. The Fuhrman nuclear grade of malignant lesions was recorded. For those patients without surgical treatment, the date of initial Bosniak classification of the cystic renal lesion(s) and the date of the last CT imaging study and last clinical note to calculate duration of imaging surveillance and duration of clinical surveillance, respectively, were used. The frequency of reclassification of Bosniak IIF lesions to Bosniak III lesions as reported by the interpreting radiologist was noted. The application of Bosniak classification by the initial interpreting radiologist was not reevaluated.

Imaging Technique

CT imaging at our institution was obtained with multidetector CT scanners (Emotion Duo, Volume Zoom, Sensation 16, or Sensation 64; Siemens Medical, Forchheim, Germany). Only patients who underwent CT imaging without contrast material and CT imaging with intravenous contrast material were included; our standard renal CT protocol included unenhanced imaging of the kidneys, followed by a 20-mL test bolus of contrast material, usually iopromide (300 mg of iodine per milliliter, Ultravist 300; Bayer Healthcare, Berlin, Germany), for arterial enhancement timing. Postcontrast imaging was performed 5 seconds after the optimal arterial time (vascular and corticomedullary phase) and then again 2 minutes after the start of contrast material injection (nephrographic phase). The specific CT parameters, contrast material injection rate, and contrast material dose were not consistent in this retrospective study. Almost all CT examinations were performed with scanners with at least four detector rows. Eight studies were performed prior to 1999 for which scanner type could not be determined.

Statistical Analysis

The homogeneity hypothesis for proportions from independent groups was assessed by using the Fisher exact test. Continuous variables were compared by using a two-tailed two-sample t test or Wilcoxon two-sample test. A statistically significant difference was considered to be indicated by a P value less than .05.

Results

Nearly all of the imaging studies (191 [99%] of 193) were interpreted by fellowship-trained abdominal radiologists; only two studies were interpreted by general practice community radiologists. The section thickness of axial CT images (170 of 178 CT examinations available for review) was 3 mm in 81% (137 of 170) of cases and 5 mm in 19% (33 of 170) of cases. Most of the CT studies (158 [82%] of 193) had multiplanar reformations available to the interpreting radiologist at the time of diagnosis.

Characteristics and treatment of patients with Bosniak IIF and Bosniak III lesions are shown in Table 1. Seventy-seven percent (101 of 131) of patients with Bosniak III lesions underwent surgical excision of the lesion(s) rather than imaging surveillance. In contrast, 21% (13 of 62) of patients with Bosniak IIF lesions underwent surgical excision. Sixteen Bosniak IIF lesions in 13 patients were resected, and six patients had a coexisting Bosniak IV lesion and/or solid renal mass (five ipsilateral and one contralateral to the Bosniak IIF lesions), three patients had a history of primary renal malignancy, two patients had an ipsilateral Bosniak III lesion, three patients requested definitive surgical treatment, and two patients had recurrent cysts after aspiration and suspicion for malignancy by the urologist. Patients with Bosniak IIF lesions were significantly more likely to undergo resection rather than imaging surveillance when there was a coexisting Bosniak IV lesion and/or solid renal neoplasm (P = .0001).

Table 1 Characteristics and Treatment of Patients with Bosniak IIF and III Lesions

^*Data in parentheses are ranges.

^†Statistically significant P value (<.05, two-sample t test).

^‡Statistically significant P value (<.05, Fisher exact test).

^§Marginally statistically significant P value (.05 < P < .10, Fisher exact test).

Nine cystic renal lesions, in eight patients, initially classified as Bosniak IIF lesions (nine [13%] of 69) were later reclassified as Bosniak III lesions at a median time of 0.5 years (range, 0.2–2.0 years) after the initial classification as a Bosniak IIF lesion (Fig 1). A single radiologist (E.M.R.) reviewed these patients’ studies and determined that morphologic changes led to reclassification of three lesions (Fig 2), Bosniak III was the appropriate original classification in four lesions (Fig 3), and Bosniak IIF was the appropriate classification in two lesions such that the lesion should not have been reclassified. Eight of these lesions were resected with a malignancy rate of 50% (four of eight). One patient had a history of contralateral partial nephrectomy for papillary RCC, was treated with periodic surveillance imaging for 1.9 years, and subsequently was lost to follow-up.

Figure 1a:

Download as PowerPointOpen in Image Viewer

Figure 1b:

Download as PowerPointOpen in Image Viewer

Figure 1c:

Download as PowerPointOpen in Image Viewer

Figure 1d:

Download as PowerPointOpen in Image Viewer

Figure 2a:

Download as PowerPointOpen in Image Viewer

Figure 2b:

Download as PowerPointOpen in Image Viewer

Figure 2c:

Download as PowerPointOpen in Image Viewer

Figure 2d:

Download as PowerPointOpen in Image Viewer

Figure 3a:

Download as PowerPointOpen in Image Viewer

Figure 3b:

Download as PowerPointOpen in Image Viewer

Figure 3c:

Download as PowerPointOpen in Image Viewer

Figure 3d:

Download as PowerPointOpen in Image Viewer

After initial CT categorization, patients with Bosniak IIF lesions underwent surgery at a median of 0.1 year (range, 0–6.1 years), and those with Bosniak III lesions underwent surgery at a median of 0.1 year (range, 0–2.1 years). Patients with either Bosniak IIF or Bosniak III lesions who underwent imaging surveillance were on average significantly older than those patients who underwent surgical excision, with a mean difference in both cases of greater than 10 years (Table 1). Clinical history that may have affected the decision to perform surgical resection such as coexisting renal lesions, history of nonrenal malignancy, and ordering physician are listed in Table 1.

The malignancy rate of and specific pathologic subtypes of resected Bosniak IIF and Bosniak III lesions are shown in Table 2. Fifty-four percent (58 of 107) of resected Bosniak III lesions were malignant and 25% (four of 16) of resected Bosniak IIF lesions were malignant, which was a significant difference (P = .03, Fisher exact test; estimated odds ratio = 3.55; 95% confidence interval: 1.08, 11.72). The Fuhrman nuclear grade was only available for three of four resected malignant Bosniak IIF lesions and was grade 1 for one lesion and grade 2 for two lesions. Fuhrman nuclear grade was available for 57 of the 58 resected malignant Bosniak III lesions and was grade 1 in 19% (11 of 57), grade 2 in 61% (35 of 57), grade 3 in 19% (11 of 57), and grade 4 in 0% (0 of 57) of lesions. Clear cell carcinoma was the most prevalent malignant neoplasm (28 [48%] of 58), and the majority of benign lesions (26 [53%] of 49) were epithelial or fibrous cysts.

Table 2 Surgical Pathologic Findings in Excised Bosniak IIF and III Lesions

Note.—Data are percentages, with numbers used to calculate percentages in parentheses. Percentages may not add up because of rounding.

^*The malignancy rate of resected Bosniak IIF and III lesions was significantly different (P = .03, Fisher exact test).

The association of three factors and the prevalence of malignancy in Bosniak IIF and Bosniak III lesions were evaluated: coexisting Bosniak III lesion, coexisting Bosniak IV lesion and/or solid mass, and a history of malignant renal neoplasm (Table 3). Two patients had both Bosniak IIF and Bosniak III lesions. The first patient had ipsilateral solitary Bosniak IIF and Bosniak III lesions with a benign cortical cyst and cystic nephroma, respectively, at surgical pathologic findings. The second had ipsilateral solitary Bosniak IIF and Bosniak III lesions and two contralateral Bosniak IIF lesions that were all benign cortical cysts according to surgical pathologic findings. For Bosniak IIF lesions, significantly more lesions were malignant when the patient had a coexisting Bosniak IV lesion and/or a solid mass. For Bosniak III lesions, any of the three factors was associated with a significantly higher percentage of malignant lesions. Two of these factors were more common in patients with Bosniak III lesions treated with imaging surveillance than resection (Table 1).

Table 3 Risk Factors for Malignancy in Resected Bosniak IIF and III Lesions

Note.—Unless otherwise indicated, data are percentages of patients, with numbers used to calculate percentages in parentheses.

^*Significant P value (<.05) by using the Fisher exact test.

Patient age was not significantly different between patients with Bosniak IIF and those with Bosniak III lesions. The median age of patients with malignant Bosniak IIF lesions (n = 4) was 62 years (range, 50–71 years), and for patients with benign Bosniak IIF lesions (n = 9), the median age was 48 years (range, 33–74 years) (P = .13, Wilcoxon two-sample test). The median age of patients with malignant Bosniak III lesions (n = 55) was 58 years (range, 27–80 years), and for patients with benign Bosniak III lesions (n = 46), the median age was 57 years (range, 33–78 years) (P = .38, Wilcoxon two-sample t test).

A history of hemodialysis was uncommon in our patient population. One patient with a single resected benign Bosniak III lesion was receiving hemodialysis, and one patient with two resected malignant Bosniak IIF lesions was receiving hemodialysis but also had a coexisting Bosniak IV lesion at the time of Bosniak classification.

The duration of imaging and clinical surveillance of Bosniak IIF and Bosniak III lesions included in the study is presented in Table 1. The majority of patients with resected Bosniak IIF (nine [69%] of 13) and Bosniak III lesions (88 [87%] of 101) had no imaging follow-up after surgery. Despite a higher percentage of patients with a coexisting Bosniak IV lesion and/or solid renal neoplasm or history of malignant primary renal neoplasm in patients with Bosniak III lesions being treated with imaging surveillance of 1 year or longer compared with surgical excision, no patient in this study developed locally advanced or metastatic disease from a cystic renal neoplasm. No Bosniak III lesions (n = 144) progressed to a Bosniak IV lesion; seven were downgraded to Bosniak IIF lesions. Median imaging follow-up was 3.8 years (range, 1.0–8.2 years), and median clinical follow-up was 4.4 years (range, 1.0–15.2 years) for patients with Bosniak III lesions managed by using imaging surveillance (Table 1).

Discussion

The Bosniak classification system is widely acknowledged as a useful guideline for managing cystic renal masses (11). The malignancy rate of 54% (58 of 107) in our patient population is consistent with the previously published and widely held belief that approximately 50% of Bosniak III lesions are malignant. While previous studies have shown a surprising variability in the percentage of malignant Bosniak III cysts (31%–100%), these numbers were based on small series that used older CT technology. A weighted average from six studies that each included more than 30 renal cystic masses found 65% of Bosniak III lesions to be malignant (12). As far as we are aware, this series of 107 resected Bosniak III lesions represents the largest report of pathologically examined Bosniak III lesions imaged by using multiphasic multidetector CT and multiphasic MR imaging examinations.

The malignancy rate of 54% in our series differs from the malignancy rate of 82% in 33 resected Bosniak III cysts found by O’Malley et al (7). The high malignancy rate was attributed to the addition of the Bosniak IIF category between the publication of older studies and the analysis. The use of the Bosniak IIF category was thought to increase the accuracy of the classification system by downgrading lesions that were not complex enough to be characterized as category III but that were more complex than category II lesions (9). There are several explanations why we may not have found as high a malignancy rate in our Bosniak III group. Because the Bosniak criteria were developed at the institution of O’Malley et al, the IIF category was more likely to have been immediately adopted, universally used, and understood. Furthermore, images in the O’Malley series were read by one of several faculty radiologists. This suggests that a small group may have evaluated these studies, leading to less observer variability. Our images were interpreted by a group of 12 fellowship-trained abdominal radiologists. While they were all well acquainted with the Bosniak classification, it is unclear how often or consistently classifications were applied because the search parameters for this study only captured lesions that were classified by using the Bosniak system. Thirteen percent of Bosniak IIF lesions were reclassified as Bosniak III lesions at surveillance imaging in our series, which is similar to the 14.8% rate in the O’Malley et al series (7), but more than the 4.8% in 48 cysts in the Israel and Bosniak series (9). Fifty percent of those that were resected were malignant. On the basis of image review, reclassification in the series was more commonly because of reader disagreement than a morphologic change in the lesion.

There was a surprisingly high malignancy rate of 25% (four of 16) in resected Bosniak IIF lesions. However, the number of resected Bosniak IIF lesions was small and only reflected a subset of Bosniak IIF lesions in the population. The patient population with resected Bosniak IIF lesions was highly selected and had a higher number of risk factors associated with malignancy than the imaging surveillance group. In our series, in patients with a Bosniak IIF lesion and a coexistent Bosniak IV lesion and/or solid mass, 71% (five of seven) of the Bosniak IIF lesions were malignant. Similarly, 67% (two of three) of Bosniak IIF lesions in patients with a history of RCC were malignant. These correlations certainly suggest that there are unaccounted for variables that could have affected the malignancy rate in resected Bosniak IIF lesions in this series.

Bosniak IIF and Bosniak III lesions encompassed a wide variety of neoplasms. While the most common malignant renal tumor in the series was clear cell carcinoma, it represented less than 50% of the malignant cystic lesions. A cystic growth pattern is seen in only 4%–15% of all RCCs (13) and occurs by four mechanisms: intrinsic unilocular cystic growth, intrinsic multilocular cystic growth, origin in the epithelium of a simple cyst, or cystic necrosis (14). True cystic growth, rather than necrosis, appears to confer a better prognosis (15). Several prior studies of cysts with Bosniak grading have concentrated on the distinction between malignant and benign lesions and have not reported the subtypes of carcinoma (3,6,8). The presumption that a malignant cystic lesion equates to a cystic clear cell carcinoma and that a benign cystic lesion equates to an epithelial cyst is false. In truth, there are a host of benign and malignant cystic renal neoplasms, including cystic clear cell carcinoma, multilocular cystic RCC, cystic nephroma, and mixed epithelial and stromal tumor of the kidney. Each confers a different prognosis and potentially requires different therapy.

We were surprised to find that 25% (15 of 58) of malignant resected cystic lesions were papillary RCCs at histopathologic examination. Typically, papillary RCC is hyperdense and homogeneously enhancing at CT (16). A papillary RCC can, however, occasionally manifest as a cystic mass. This has been attributed to inherent architecture or secondary to cystic degeneration and extensive necrosis (17). One series found that cystic degeneration was almost as likely to occur in papillary RCC as in clear cell RCC (18). In addition, some papillary RCC are known to enhance only minimally after intravenous contrast material administration. These minimally enhancing tumors may have been mistaken for cystic lesions at the time of image interpretation, especially if near water attenuation was measured on precontrast CT images.

Clinical data and CT image findings strongly affected the risk of malignancy for complex cysts in this study. Seventy-one percent (five of seven) of Bosniak IIF lesions found in patients with a coexisting Bosniak IV lesion and/or solid renal mass were malignant, which occurred significantly more often than if either of these findings was not present. The percentage of Bosniak III lesions that were malignant was especially high when associated with other Bosniak III lesions in the same patient (10 [83%] of 12), a coexisting Bosniak IV lesion and/or solid renal mass (15 [83%] of 18), or a history of RCC (eight [100%] of eight). This suggests that patient-related factors that predispose to RCC may be at work in these patients. As with all Bosniak III cystic renal lesions, surgery should be first-line management. If there are contraindications to surgery, imaging follow-up is a reasonable approach.

None of the patients with Bosniak IIF or Bosniak III lesions in this study (n = 193) had progression to Bosniak IV lesions or solid neoplasms, and none developed locally advanced or metastatic disease. If there is a continuous spectrum such that some Bosniak III lesions progress to Bosniak IV lesions, the rate of progression was too low to be captured in our series. Despite a higher number of potential risk factors associated with malignant Bosniak III lesions in the imaging surveillance group (n = 30), none of these consequences were detected with imaging follow-up for a median of 3.8 years (range, 1.0–8.2 years) and clinical follow-up for a median of 4.4 years (range, 1.0–15.2 years).

Although the rate of development of metastatic disease found at short-term imaging surveillance for Bosniak IIF and Bosniak III lesions was 0% (0 of 193), the long-term rate of development of metastatic disease remains unknown. Despite a malignancy rate of more than 50% for Bosniak III lesions, there is no prospective data to show that resection improves survival. Given that nearly half of Bosniak III lesions are benign and that the risk of metastatic disease or local progression appears to be low, our data support current recommendations for observation in patients with Bosniak IIF or Bosniak III lesions and multiple comorbidities or short life expectancy (19).

There were a number of limitations of our study. First, it was a retrospective case series; therefore, there was no standardized follow-up interval and there were changes in CT technology during the time interval of the study. Second, there were multiple readers who interpreted the CT images that were included in the study. Application of the Bosniak classification system is subjective, and the agreement between observers evaluating the features that are used to select a Bosniak category (20) and agreement between category assignments (6) have been previously evaluated. A choice was made not to reinterpret studies by using expert readers, with the hope that this series would represent a real-world experience, not an idealized one. Third, we have no way of knowing how often or consistently Bosniak criteria were applied to all cystic renal lesions encountered at CT imaging, because the search parameters for this study only captured lesions that were classified by using the Bosniak system. Fourth, for patients with resected Bosniak IIF lesions, the statistical power to associate malignant Bosniak IIF lesions with risk factors such as coexisting Bosniak III lesion or history of RCC was limited by patient sample size, and the lack of a significant P value does not include or exclude an important clinical association (Table 3). Fifth, in lesion-level analyses (Table 2), multiple lesions within patients were treated as statistically independent; therefore, any intrapatient correlation due to clustering was not accounted for in hypothesis tests. We note that 23% (three of 13) of patients with surgically excised Bosniak IIF lesions and 8% (eight of 101) of patients with surgically excised Bosniak III lesions had more than one Bosniak IIF or Bosniak III lesion, and only one patient had more than three. Last, the true malignancy rate of the Bosniak IIF and Bosniak III lesions in patients who underwent imaging surveillance is not known, and the length of imaging follow-up may have been insufficient to detect imaging manifestations of malignancy.

In conclusion, 54% (58 of 107) of Bosniak III cystic renal lesions were malignant in our series, with clear cell carcinoma and papillary RCC most common. Thirteen percent (nine of 69) of Bosniak IIF lesions were reclassified at follow-up and 50% (four of eight) of these patients had malignant lesions. A history of primary renal malignancy, coexisting Bosniak IV cystic renal lesion and/or solid renal mass (common in patients with resected Bosniak IIF cystic renal lesions), and multiplicity of Bosniak III cystic renal lesions were all associated with an increased risk of malignancy in Bosniak IIF and Bosniak III cystic renal lesions. None of the patients with Bosniak IIF or III cystic renal lesions in this study had progression to Bosniak IV lesions or solid renal neoplasms, and none developed locally advanced or metastatic disease.

Disclosures of Potential Conflicts of Interest: A.D.S. No potential conflicts of interest to disclose. E.M.R. No potential conflicts of interest to disclose. K.L.C. No potential conflicts of interest to disclose. M.L.L. No potential conflicts of interest to disclose. B.C.A. No potential conflicts of interest to disclose. S.N.S. No potential conflicts of interest to disclose. B.R.H. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution has grant from Siemens Medical for radiation dose research. Other relationships: none to disclose.

Author Contributions

Author contributions: Guarantors of integrity of entire study, A.D.S., E.M.R.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, A.D.S., E.M.R., K.L.C., S.N.S., B.R.H.; clinical studies, A.D.S., E.M.R., S.N.S.; statistical analysis, A.D.S., K.L.C., M.L.L.; and manuscript editing, all authors