DOI:10.2214/AJR.07.3181
AJR 2008; 191:1559-1563
© American Roentgen Ray Society
Differentiation of Pathologic Subtypes of Papillary Renal Cell Carcinoma on CT
Takayuki Yamada1,
Mareyuki Endo2,3,
Masahiro Tsuboi4,
Toshio Matsuhashi1,
Kei Takase1,
Shuichi Higano1 and
Shoki Takahashi1
1 Department of Diagnostic Radiology, Tohoku University Hospital, Tohoku
University Graduate School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai,
Miyagi 980-8574, Japan.
2 Department of Pathology, Tohoku University Hospital, Miyagi, Japan.
3 Present address: Department of Pathology, Sendai Kosei Hospital, Miyagi,
Japan.
4 Department of Radiology, Osaki Municipal Hospital, Miyagi, Japan.
Received September 18, 2007;
accepted after revision May 10, 2008.
Address correspondence to T. Yamada
(yamataka{at}rad.med.tohoku.ac.jp).
Abstract
OBJECTIVE. We reviewed the CT findings of the subtypes of papillary
renal cell carcinoma (RCC), which behave differently
clinicopathologically.
CONCLUSION. The CT features of the two pathologic subtypes of
papillary RCC differ, probably reflecting their different pathologic features.
Type 1 tumors have more distinct margins than type 2 tumors and have
homogeneous density. Although type 2 tumors in the early stages show findings
similar to those of type 1 tumors, they are at more advanced stages on the
whole, with CT features showing indistinct margins, frequent centripetal
infiltration, and tumor thrombi in all pT3b cases. Radiologists should be
familiar with the CT features of papillary RCC that suggest different
pathologic behaviors, such as tumor stage, tumor proliferation, and
microvascular or vascular invasion.
Keywords: CT • kidney disease • oncologic imaging • papillary renal cell carcinoma • renal cell carcinoma
Introduction
Papillary renal cell carcinoma (RCC) accounts for approximately 10% of RCCs
[1]. Pathologically, papillary
RCC is recognized as a distinct tumor type. However, Delahunt and Eble
[2] further defined papillary
RCC into two subtypes, type 1 and type 2, on the basis of histology. Type 1
tumors have papillae covered by small cells with scant cytoplasm arranged in a
single layer on the papillary basement membrane
(Fig. 1A). Type 2 tumor cells
are often of higher nuclear grade than type 1 tumor cells with eosinophilic
cytoplasm and pseudostratified nuclei on papillary cores
[3]
(Fig. 1B). Investigators have
reported that the two subtypes of papillary RCC are correlated with specific
genetic abnormalities [4].
Furthermore, these two subtypes show different clinicopathologic behaviors:
Type 2 tumors are associated with a poorer prognosis than type 1 tumors and
even than clear cell RCC [5,
6].
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Fig. 1A —Typical pathologic features of papillary renal cell
carcinoma. Type 1 tumor of 41-year-old man. Photomicrograph shows tumor has
papillae covered by small cells arranged in single layer on papillary
membrane. Foamy cells are prominent. (H and E)
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Fig. 1B —Typical pathologic features of papillary renal cell
carcinoma. Type 2 tumor of 78-year-old man. Photomicrograph shows
pseudostratified nuclei on papillary cores and nucleolus formation. (H and
E)
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Papillary RCC has been investigated radiologically. An early report
indicated that selective renal arteriograms showed very hypovascular or
avascular tumors in all cases of RCC
[7,
8]. However, the enhancement
patterns differ among the subtypes of RCC on dynamic CT
[9]. Papillary RCC is typically
hypovascular and homogeneous
[10] and shows less
enhancement than the clear cell subtype during the corticomedullary phase on
dynamic CT studies [9]. On MRI,
papillary RCC tends to show homogeneous signal intensity and
characteristically shows hypointensity on T2-weighted images
[11,
12].
In most radiologic studies, researchers have evaluated papillary RCC as a
single subtype
[7–11].
In one radiology report, investigators presented MR images with a caption
mentioning the subtype of papillary RCC; however, they did not present an
adequate discussion about the differences in MRI findings between the subtypes
[12]. Thus, radiologic
differentiation of the two subtypes of papillary RCC remains unresolved. In
this study, we examined the differences in the CT features of types 1 and 2
papillary RCCs.
Materials and Methods
Subjects
We found the records of 20 consecutive patients in the pathologic reporting
system at two hospitals who had been diagnosed with papillary RCC between
January 2000 and May 2007. Ethics committee approval was not required because
this study was a retrospective review of clinical cases. Nineteen patients had
undergone preoperative CT in our hospitals and the images were available. One
patient had undergone CT in another hospital and the images were not
available; that patient was excluded from the present study. Thus, the study
group consisted of 19 patients, 18 men and one woman, who ranged in age from
41 to 78 years (median, 58 years). One patient had two discrete tumors in the
ipsilateral kidney that were identified on CT. There fore, 20 tumors were
examined in this study.
Pathologic Evaluation
One experienced pathologist who was unaware of the clinical information
associated with each case reviewed the slides and classified the tumors into
the pathologic subtypes of papillary RCC: type 1 or type 2. The pathologic
tumor stage (pT) was recorded according to TNM classification
(Table 1).
CT Examination
Because each CT examination was performed at different times over a period
of 7 years, the patients were examined using various types of helical CT
scanners. Unenhanced and triphasic contrast-enhanced CT examinations were
performed in 15 patients (17 tumors). These CT images were obtained with the
following para meters: 120 kVp; reconstruction interval, 5 mm in the
corticomedullary and nephrographic phases; and reconstruction interval, 10 mm
in the unenhanced and excretory phases. For the contrast-enhanced studies, 100
mL of nonionic iodine contrast material at a concentration of 300 mg I/mL was
injected into an antecubital vein at a rate of 3.0 mL/s using a mechanical
injector. Scanning for the corticomedullary phase was started 30 seconds after
contrast injection. The nephrographic phase started 90 seconds after contrast
injection, and the excretory phase started 180 seconds after contrast
injection. Only unenhanced and monophasic contrast-enhanced scans were
obtained in one patient with a type 1 tumor and three patients with type 2
tumors. CT was performed using the same parameters as described earlier except
the reconstruction inter val was 10 mm. The injection rate of IV contrast
material was 1.0 mL/s. Scanning for contrast-enhanced CT was started from the
liver 90 sec onds after beginning contrast injection. Because the renal
parenchyma enhanced well, contrast-enhanced CT was substituted for
nephrographic phase scanning.
Image Interpretation
Three radiologists who were unaware of the subtype of papillary RCC
reviewed the CT images. Each radiologist had at least 7 years of clinical
experience. They recorded the margins, homogeneity, and tumor thrombi by
consensus. The margin was evaluated in the nephrographic phase or excretory
phase in which the tumor margin was discriminated by the homogeneously
enhanced renal parenchyma. When the tumor was interpreted as infiltrating
beyond the renal parenchyma centripetally or centrifugally, the margin was
interpreted as indistinct. The reviewers measured the longest tumor diameter
on the contrast-enhanced scans and the CT attenuation on unenhanced images,
corticomedullary phase images, and nephrographic phase images. A round region
of interest was placed to cover as much of the solid enhancing area as
possible. The relative enhancement ratio was calculated for the
corticomedullary phase and nephrographic phase. The relative enhancement ratio
for the cortico medullary phase was calculated as follows:
 |
where TCMP is the attenuation of the tumor during the
corticomedullary phase and Tpre is the attenuation of the
tumor before contrast administration. The relative enhancement ratio for the
nephrographic phase was calculated as follows:
where TNP is the attenuation of the tumor during the
nephrographic phase.
In one case of each subtype, we were able to review sequential CT
examinations retro spectively. The follow-up time was 2 years for the type 1
tumor and approximately 1 year for the type 2 tumor. We assessed the initial
tumor stage and tumor growth during these periods on CT scans.
Statistical Analysis
The pathologic and CT findings of the subtypes of papillary RCC were
compared statistically. Contingency tables and Fisher's exact test were used
to evaluate the pathologic tumor stage and the tumor margins and heterogeneity
on CT scans. The Mann-Whitney U test was used to evaluate the
diameter, CT attenuation on the unenhanced scans, and relative enhancement
ratio. The relative enhancement ratio was compared for the 17 tumors that
underwent triphasic contrast-enhanced CT examination. A p value of
less than 0.05 was considered to indicate statistical significance.
Results
Pathologic Review
Twelve tumors were classified as type 1 and eight as type 2. The type 1
tumors were staged as pT1 in 10 patients, pT2 in one patient, and pT3a in one
patient. The type 2 tumors were staged as pT1 in two patients, pT3a in one,
and pT3b in five.
CT Findings
CT showed that type 1 tumors typically have distinct margins and
homogeneous internal density (Fig.
2A,
2B). Even the one type 1 tumor
at stage pT3a maintained those radiologic features (Fig.
3A,
3B). The margins of the type 1
tumors were more frequently distinct than those of type 2 tumors (p =
0.004) (Table 2). The
heterogeneity of tumor density did not differ significantly between the two
subtypes (p = 0.062) (Table
2).
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Fig. 2A —62-year-old woman with type 1 papillary renal cell carcinoma.
Pathologic tumor stage is pT1a. Contrast-enhanced CT scan shows tumor in right
kidney with distinct margins and homogeneous intratumoral density.
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Fig. 2B —62-year-old woman with type 1 papillary renal cell carcinoma.
Pathologic tumor stage is pT1a. Obtained 2 years after A,
contrast-enhanced CT scan shows tumor in right kidney has enlarged slightly,
but distinct margins and homogeneous intratumoral density are preserved.
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Fig. 3A —68-year-old man with type 1 papillary renal cell carcinoma.
Pathologic tumor stage is pT3a. Unenhanced CT scan shows tumor in right
kidney. Although tumor minimally infiltrates perirenal space pathologically,
margin is distinct radiologically and internal density is homogeneous.
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The longest diameter ranged from 1.8 to 10 cm (mean, 3.3 cm) in type 1
tumors and from 2.2 to 8.2 cm (mean, 5.1 cm) in type 2 tumors. The type 2
tumors were significantly larger than the type 1 tumors (p = 0.037).
The mean attenuation on the unenhanced CT scans did not differ significantly
for type 1 and 2 tumors (34.6 and 38.4 HU, respectively; p = 0.44)
(Table 2). The tumors of both
subtypes showed minimal enhancement. The mean relative enhancement ratios in
the corticomedullary phase and nephrographic phase of type 2 tumors (0.63 and
0.85, respectively) were slightly higher than those of type 1 tumors (0.41 and
0.51, respectively). However, the difference was not significant (p =
0.496 and 0.267) (Table 2).
Type 2 tumors were generally more advanced than type 1 tumors at the time
of diagnosis, as shown in the pathologic results. CT showed tumor thrombi in
all cases at pT3b and infiltrating tumor centripetally or centrifugally beyond
the renal parenchyma. Despite the more advanced stages and larger sizes of
type 2 tumors, the renal cortex in the vicinity of the centripetal tumor was
characteristically preserved (Figs.
4A,
4B,
5A,
5B,
6A,
6B,
6C,
6D and
Table 2).
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Fig. 4A —Illustrations show renal cortex is preserved in papillary
renal cell carcinoma. Type 1 tumor. Distinct tumor is noted in renal
parenchyma, adjacent to which renal capsule (dashed line) is intact.
Renal cortex in vicinity is preserved.
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Fig. 4B —Illustrations show renal cortex is preserved in papillary
renal cell carcinoma. Type 2 tumor. Indistinct tumor involving renal cortex
(asterisk) infiltrates centripetally. Despite more advanced stages
and larger size of type 2 tumor, renal cortex in vicinity is frequently
preserved as well as in type 1 tumors. Tumor extends beyond renal capsule
(dashed line).
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Fig. 5A —73-year-old man with type 2 papillary renal cell carcinoma.
Pathologic tumor stage is pT3b. Large hypodense tumor in right kidney is
recognized in nephrographic phase. Note delay in contrast in right kidney
compared with left kidney. Corticomedullary contrast still remains in right
kidney, unlike left kidney. True margin between tumor and renal parenchyma is
not indicated; tumor extends into central region as well as perirenal space.
Cortex (arrow) in vicinity of tumor is preserved.
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Fig. 5B —73-year-old man with type 2 papillary renal cell carcinoma.
Pathologic tumor stage is pT3b. Image shows tumor margins of infiltrating
component (arrow) are indistinct. Tumor density is somewhat
heterogeneously hypodense.
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Fig. 6B —78-year-old man with type 2 papillary renal cell carcinoma.
Pathologic tumor stage is pT3b. Contrast-enhanced CT scan obtained 7 months
after A in nephrographic phase shows enlargement of tumor
(arrow) in right kidney.
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Fig. 6C —78-year-old man with type 2 papillary renal cell carcinoma.
Pathologic tumor stage is pT3b. Contrast-enhanced CT scan obtained 14 months
after A in nephrographic phase shows heterogeneously hypodense tumor
infiltrating right renal vein.
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Fig. 6D —78-year-old man with type 2 papillary renal cell carcinoma.
Pathologic tumor stage is pT3b. Multiplanar reformat image shows
heterogeneously hypodense tumor forming tumor thrombus in right renal vein.
Preserved cortex (arrows) is recognized. Contrast-enhanced CT scan
shows hypodense tumor infiltrating right renal vein. Growth rate of type 2
tumor is faster than that of type 1 tumor, as shown in Figure
3A,
3B. F = foot, L = left.
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We were able to review sequential CT examinations in one type 1 tumor and
one type 2 tumor. The type 1 tumor grew slowly over 2 years (Fig.
3A,
3B). The initial tumor stage
was T1a and did not change. By contrast, the type 2 tumor was initially staged
as T1a (Fig. 6A) and was
difficult to differentiate from type 1 tumors. However, this tumor had grown
larger (Fig. 6B), infiltrated
centripetally, and formed a tumor thrombus in the renal vein over a shorter
period (
1 year) than the type 1 tumor. Preserved cortex was noted in the
vicinity of the tumor (Figs.
6C and
6D).
Discussion
Our results indicate that type 1 and 2 papillary RCC tumors can be
differentiated from one another to an extent on CT but that they sometimes
show similar radiologic features, especially in the early stages.
An enhancement pattern suggesting a hypovascular tumor is recognized in
both subtypes of papillary RCC, which means that the enhancement pattern is
not useful for discriminating between the subtypes. This finding is compatible
with those of some previous reports in which the investigators stated that
papillary RCC is typically hypodense and homogeneous
[9,
10] and that a high
tumor-to-parenchyma enhancement percentage (> 25%) essentially excludes the
possibility of papillary RCC
[10].
In our series, most type 1 tumors had distinct margins, whereas type 2
tumors showed significantly more indistinct margins with infiltrative growth.
Type 2 tumors typically showed heterogeneous density when compared with type 1
tumors with a marginal significance level (p = 0.062). The type 2
tumors were significantly larger than the type 1 tumors (p = 0.037)
and were at more advanced stages, frequently infiltrating centrally to form
the tumor thrombus. Such differences in the image findings between the
subtypes of papillary RCC may not be surprising when the pathology reports are
considered [2,
5]. In one large series, most
type 1 tumors were classified as pT1 or pT2, whereas approximately half of the
type 2 tumors were pT3 or pT4
[2].
In consideration of the more advanced stages and larger sizes of type 2
tumors in our series, the renal cortex in the vicinity of the type 2 tumors is
relatively preserved. Initially, these type 2 tumors would have developed in
the proximal tubules and involved the renal cortex; thereafter, the tumor
might have extended centripetally to the renal vein rather than infiltrating
the surrounding renal cortex, thus leaving preserved cortex in the vicinity. A
recent pathologic analysis revealed that type 2 tumors were associated with
microvascular or vascular invasion significantly more often than type 1 tumors
[6,
13]. The propensity of type 2
tumors for extending to the renal vein seen in our study could reflect such
pathologic characteristics.
Type 2 tumors in the early stages showed CT findings similar to those of
type 1 tumors, whereas type 2 tumors in the advanced stages showed centripetal
extension with tumor thrombi. In one case each of type 1 and 2 tumors that
were followed up in our study, the type 2 tumor grew faster than the type 1
tumor. The type 2 tumor increased in size and invaded the renal vein within 1
year; in contrast, the type 1 tumor was relatively stable in size for 2 years.
Although this difference in progression may not be generalized, it could
reflect differential aggressiveness of the two types: Type 2 tumors may have a
more aggressive nature than type 1 tumors, which is suggested by pathologic
and urologic reports of significantly higher levels of proliferation markers
in type 2 tumors [5] and the
propensity of microvascular invasion of type 2 tumors
[6]. The difference in growth
could result in type 2 tumors being more advanced at the time of diagnosis
than type 1 tumors.
Our study was limited in that the number of cases was relatively small.
Although more cases of papillary RCC were evaluated in our study than in
previous radiology reports that evaluated enhancement patterns on CT, we still
studied fewer cases than were studied in pathology reports.
Selection of the surgical procedure may depend not on the pathologic
subtype but on the stage of the primary renal tumor. Preoperative
discrimination of the subtype of papillary RCC may not be crucial. In the
radiology literature, papillary RCC has been described as a single entity that
has a favorable outcome [9,
10]. Indeed, the CT findings
previously described in the radiology literature probably represent type 1
tumors. In the figures included in those reports, the tumor stage appeared to
be T1a because the tumor margins were distinct and the internal density was
homogeneous [9,
10]. However, in recent
urologic studies, researchers suggested that papillary tumors are a
heterogeneous group of entities and reported that type 2 tumors show more
advanced pathologic features and are associated with a poorer survival than
type 1 tumors and clear cell RCC
[6,
13].
In our study, a series of papillary RCC cases showed a variety of CT
features: Type 1 tumors had more distinct tumor margins and homogeneous
internal density, whereas type 2 tumors had less distinct tumor margins and a
propensity for centripetal infiltration with frequent tumor thrombus.
Therefore, we believe that radiologists should be aware that papillary RCC
cases appear as two types with different pathologic behaviors, including tumor
stage, tumor proliferation, and microvascular or vascular invasion.
In conclusion, our results indicate that CT may help radiologists
differentiate type 1 from type 2 papillary RCC tumors, which have different
pathologic behaviors and prognoses.
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Abstract
Introduction
