Download Alveolar Architecture of Clear Cell Renal Carcinomas «5.0 cm

Jpn J Clin OncoI1999;29(4 )198-203
Alveolar Architecture of Clear Cell Renal Carcinomas «5.0 cm)
Show High Attenuation on Dynamic CT Scanning
Hiroyuki Fujimoto1, Fumihiko Wakao 2, Noriyuki Moriyama2, Kenichi Tobisu1, Michiie Sakamoto3 and
Tadao Kakizoe 1
Departments of 1Urology and 2Diagnostic Radiology, National Cancer Center Hospital and 30ivision of Pathology,
National Cancer Center Research Institute, Tokyo, Japan
Background: Toestablish the correlation between tumor appearance on CT and tumor histology
in renal cell carcinomas.
Methods: The density and attenuation patterns of 96 renal cell carcinomas, each :::;5 cm in
greatest diameter, were studied by non-enhanced CT and early and late after bolus injection of
contrast medium using dynamic CT. The density and attenuation patterns and pathological maps
of each tumor were individually correlated.
Results: High attenuated areaswere presentin 72 of the 96 tumors on early enhanced dynamic
CT scanning. All 72 high attenuated areas were of the clear cell renal cell carcinoma and had
alveolar architecture. The remaining 24 tumors that did not demonstrate high attenuated foci on
early enhanced scanning included three clear cell, nine granular cell, six papillary, five
chromophobe and onecollecting ducttype.Withrespect to tumorarchitecture, allclearcelltumors
of alveolar architecture demonstrated high attenuation on early enhanced scanning.
Conclusion: Clear cell renal cell carcinomas of alveolar architecture show high attenuation on
early enhanced dynamic CT scanning. A largernumber of patients are indispensable to obtaining
clear results. However, these findings seem to be an important clue to the diagnosis of renal cell
carcinomas as having an alveolar structure.
Key words: renal cell carcinoma - computed tomography - attenuation
INTRODUCTION
Recently, the wide use of computed tomography (CT) and
trans-abdominal ultrasound have allowed earlier detection of
small renal tumors 0-3). A common radiological characteristic
of renal cell carcinomas is increased vascularity. Selective renal
arteriography has been performed to estimate tumor vascularity
as the final and definitive diagnostic step in the evaluation oflarge
renal masses (4). However, the histological architectures representing radiological features such as arteriovenous fistulae and
pooling of contrast media have not been definitively determined.
Dynamic thin-section CT with administration of contrast medium
by bolus peripheral injection has been reported to be superior to
conventional enhanced CT in evaluating tumor vascularity (5,6).
If a correlation between tumor vascularity and tumor morphology
can be established, a more precise diagnosis of renal cell
carcinoma and different diagnosis between renal cell carcinoma
Received November 5, 1998; accepted December 28, 1998
For reprints and all correspondence: Hiroyuki Fujimoto, Division of
Urology, National Cancer Center Hospital, 1-1, Tsukiji 5 chome, Chuo-ku,
Tokyo,I04-0045,Japan
from other renal masses including oncocytoma, angiomyolipoma
with low content of lipid structure, complicated cyst and benign
mesenchymal tumor may be achieved preoperatively. In an
attempt to evaluate this correlation, the density and attenuation
patterns of 96 renal cell carcinomas were studied.
MATERIALS AND METHODS
PATIENTS
A total of 96 renal cell carcinomas with individual diameters of
:::;5 ern from 96 consecutive patients with renal cell carcinomas
were evaluated between January 1990 and April 1997. The larger
renal cell carcinomas tend to have the more heterogeneous
architecture, thus leading to 'misunderstanding of the accurate
correlation between tumor mapping and CT findings. For the first
steps of this analysis, renal cell carcinomas :::;5 em in greatest
diameter were selected. Patients were subjected to dynamic CT
scanning followed by radical or partial nephrectomy. All
specimens were examined by step-section. The size of the tumors
ranged from 1.3 to 5 cm (mean 3.5 ern). Tumor size was
determined using the greatest diameter of the freshly excised
specimens.
© 1999 Foundation for Promotion of Cancer Research
Jpn J Clin OncoI1999;29(4)
D isO
199
.markedly
-low
. low
Diso
Dhigh
D low
Figure 1. IT density patterns in plain (A) and attenuation pattern in early enhanced (B) and late enhanced (C) scans were classified as markedly low,low, iso or high
in comparison with the renal medull a. The lower half is a schematic illustration.
cr TECHNIQUE
A NALYSIS OF C ORRELATION BETWEEN T UMOR M ORPHOLOGY
AND
The initial scan was performed without contrast medium (plain
scan) . To obtain the early enh anced scan, scanning was begun
30--40s after machine-injected bolus administration of 100-1 20 ml
of contrast medium (injection rate 2.5-3.0 ml/s). The equipment
used was a Toshiba X-Vigor with 7 rum/second table feed for
7 mm slice helical (spiral ) scans (6). Additional scanning was
carried out to 5-7 min after initial injection of contrast medium
to record late enhancement (late enh anced scan). Tumor density
in plain scan and tumor attenuation in early and late scan were
classified as markedly low, low, iso and high in comparison with
that of renal medulla (Fig. 1).
P ATHOLOGICAL ANALYSI S
Horizontal step-sectioning of excised kidne y at - 1 ern width was
adopted to compare the pathological finding s with CT findings.
Macro scopic views of the greatest diameters were recorded
photographi cally. Histopathological whole mapping of the
greatest diameters was carried out in accordance with the Arme d
Forces Institute of Pathology (APIP) classification of renal cell
carcinoma (7). In this classification, cell types are listed as clear
cell, granular cell (chromophilic), papillary, chromophobe ce ll,
sarcomatoid and collecting duct and morph ological architecture
as alveolar, acinar and cystic in clear cell renal cell carcinom a.
The tumor grade was determined by Fuhrman 's grading system
(8). The 96 tumors were classified as follows: 75 clear cell, nine
granular cell, six papillary, five chromophobe cell and one
collecting duct type. No sarcomatoid tumors were present in this
series.
CT
FINDINGS
If the tumor showed heterogeneous attenuation on early scan,
three isolated high, iso or low attenuation areas on early enhanced
scanning of that tumor 's greatest diameter were exc ised and three
areas (about 2-3 mm 2) were selected for analysis. If the tumor
show ed homogeneous attenuation, 1-3 random areas were
selected to assess the histological difference. The density pattern s
on plain scanning and the attenuation pattern on late enhanced
scanning of these same areas were examined. Following whole
mapping of each tumor, tumor morphology and the CT finding s
were correlated. Because a single tumor had up to three different
evaluable areas on CT scanning, a total of 189 areas from 96
tumors were analyzed in this series. Although the cell type of a
given tumor was uniform, the cell architecture within a single
tumor varied in accordance with the CT fmdings described below.
RESULTS
In the early enhanced scans, 72 (75%) of96 tumors demonstrated
at least one high attenuated area. The remaining 24 (25 %) tumors
did not demonstrate any areas of high attenuation. All 72 high
attenuated tumors were clear cell rumors. The remaining 24
tumors included three clear cell, nine granular cell, six papillary,
five chromophobe and one collecting duct type. Out of a total of
75 clear cell tumor s observed in this series, only three did not
show high attenu ated areas on the early enhanced scanning. Of
these three clear cell tumors, two had an acinar structure without
alveolar architecture and the remaining tumor had a solid
architecture.
CT findings in the early enhanced scans showed a good
correlation with gross findings and pathological mapping of the
200
Dynamic CT of renal cell carcinoma
D
D
alveolar.grade 1
cystic.grade 1
normal
kidney
Figure 2. Correlation betweendensity patternon dynamicCT in plain (A)and attenuation pattern in early enhanced (B)and lateenhanced (C) scan, macroscopic view
(D) and pathological mapping (E).
o
18
o
alveola r, grade 1
alveo-acinar, grade 2
acinar, grade 1
Figure 3. Clearcell renalcell carcinoma,The attenuation patternon enhancedCTand tumor morphologyexhibiteda goodcorrelation, Alveolarstructure demonstrates
high attenuation arid cystic lesions demonstrate low attenuation in early enhanced scans.
high attenuated tumors (Figs 2 and 3). The 189 identified areas
included clear cell tumors of the following architectures: 100
alveolar, 35 acinar and 20 cystic . The remaining 34 areas included
six papillary cell tumors of a papillary and one of a papilla-acinar
structure, seven granular cell tumors of alveolar structure , five
chromophobe cell ' tumors of broad alveoli architecture, one
collecting duct tumor of dilated tubule architecture (7) and 14
fibrotic or necrotic lesions .
Jpn J Clin OncoI1999;29(4)
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Table 1. Correlation of non-enhanced CT density with histology and tumor density
CT density
Cell type
Tumor architecture
Low
Iso
High
Clear
Alveolar
23/100 (23.00%)
77/100 (77.0%)
0/100
Acinar
20/35 (57.1%)
14/35 (40.0%)
1/35 (2.9%)
Cystic
14/20 (70.0%)
6/20 (30%)
0/20
Papillary
Papillary
0/7
1/7 (14.2%)
6/7 (85.7%)
Granular
Alveolar arrangement
0/6
6/6 (100%)
0/6
Chromophobe
Broad alveoli
0/5
5/5 (100%)
0/5
Collecting duct
Dilated tublus
1/1 (100%)
0/1
0/1
On unenhanced scanning, 85.7% papillary renal ceII carcinoma demonstrated high density. Almost all other tumors showed iso or low density.
Table 2. Correlation of tumor attenuation with histology
Cell type
Attenuation in early-late scan on enhanced dynamic CT
Tumor architecture
Low-m.low*
Clear
Low-low
Iso-m.low*
Alveolar
0
0
0
Acinar
a
0
0
4/20 (20%)
0
Cystic
16/20 (80.0%)
Iso-low
3/100 (3/0%)
35/35 (l 00%)
0
High-low
97/100 (97%)
0
0
Papillary
Papillary
a
a
0
7/7 (100%)
0
Granular
Alveolar arrangement
0
1/6 (100%)
0
5/6 (83.3%)
0
Chromophobe
Broad alveoli
0
0
0
5/5 (100%)
0
Collecting duct
Dilated tubulus
a
0
1/1 (100%)
a
0
Only clear cell tumors of alveolar architecture demonstrated high attenuation on early enhanced scanning. Granular, chromophobe, papillary and colIecting duct types
of renal cell carcinomas demonstrated iso-attenuation in early enhanced scans except for one granular tumor with low attenuation. Fibrosis and necrosis are excluded
from this table. *Markedly low.
The density patterns in plain scan and the attenuation patterns
in early and late scan of these 175 areas (all except the 14 fibrotic
or necrotic lesions) are shown in Tables 1 and 2. On plain scans,
6n (85.7%) papillary and one acinar clear cell tumors revealed
high density. Almost clear cells showed low or iso-density on
plain scan. On early enhanced scanning, only clear cell tumors of
alveolar structure demonstrated high attenuation. Ninety seven
(97.0%) of 100 lesions with alveolar structure revealed high
attenuation in early enhanced scans and low attenuation in late
enhanced scans. All acinar structure tumors showed iso-attenuation in early enhanced scans and low attenuation in late enhanced
scans. Sixteen (80%) of 20 cystic tumors exhibited low attenuation in early enhanced scans and markedly low attenuation in late
enhanced scans. Papillary (Fig. 4), granular (Fig. 5) and
chromophobe (Fig. 6) types demonstrated iso-attenuation in early
scan. There were no high attenuated cell types except clear cell
types. There was no definite correlation between tumor grade and
tumor attenuation.
DISCUSSION
Most renal cell carcinomas are well known to be hypervascular
tumors on angiography (4). However, an accurate correlation
between tumor vascularity and pathological architecture has not
been established. In analyzing 96 renal cell carcinomas ~5 cm in
diameter, it was found that the attenuation pattern on early
enhanced dynamic CT scanning correlated well with tumor cell
type and pathological architecture. Only clear cell tumors with
alveolar architecture demonstrated high attenuation compared to
that of renal medulla on early enhanced scanning. Tumors with
acinar architecture had almost the same attenuation as that of
renal tubules. Cystic tumors showed low attenuation in early
enhanced scans and markedly low attenuation in late enhanced
scans. These results led us to conclude that the hypervascularity
of most renal cell carcinomas on early dynamic CT scanning is
due to the alveolar architecture of clear cell tumors in small
(~5.0 em ) renal cell carcinoma. A few clear cell tumors did not
included areas of alveolar architecture and that is why these
tumors did not demonstrate high attenuated lesion. For iso-attenuated tumors, it is difficult to reach an accurate diagnosis from the
attenuation pattern of dynamic CT. Iso-attenuated tumors included papillary, chromophobe, granular, collecting duct and rare
clear cell types. In our series, six of seven papillary tumors were
iso-attenuation tumors on early enhanced scanning and showed
high density on plain CT. High density on non-enhanced CT
scanning may be one of the characteristics of papillary renal cell
carcinomas. No other features of these tumors were established.
202
Dynamic CT of renal cell carcinoma
D
Ii]
papillary, grade 2
papillo-acinar, grade 2
Figure 4. Papillary renal cell carcinoma. In plain scan the tumor showed high density and no high attenuation in early scan.
®
D
alveolar arrangement, G3
Figure S. Granular renal cell carcinoma. In early scan the tumor was homogeneous and showed no high attenuation.
Analysis of CT number may be useful in theses iso-density
tumors.
Fairly recently, Thoenes et al. (9) reported a new classification
system for renal cell carcinoma including chromophobe cell
tumors. According to their classification based on the histogenesis of renal cell carcinomas, the clear cell type is derived from
renal proximal tubules whereas the chromophobe cell type comes
from distal tubules . In early dynamic CT scanning, clear cell
tumors of alveolar architecture demonstrated a high attenuation
that was almost equal to the attenuation of renal cortex . In
contrast, the chromophobe cell type showed iso-attenuation with
the renal medulla and had lower attenuation than the renal cortex .
These phenomena may explain the good correspondence with
tumor vascularity and histogenesis reported by Thoenes et al.
Recent cytogenetic studies have revealed that papillary and
chromophobe cell tumors are special types of renal cell carcino-
Jpn J
cu« Oncol1999 ;29(4 )
203
®
D
broad alveoli
normal
parenchyma
Figure 6. Chromophobe renal cell carcinoma. In the plain scan, the tumor showed iso-density and in early scan iso-auenuation.
rna ( 10- 12). Clinically, our data suggest that the vascularity of
clear cell renal carcinomas differs from that of non-clear cell renal
carcinom as. Considering these density and attenuation patterns,
.clear cell tumors appear to be a different entity from other variants
of renal cell carcinoma such as papillary, chromophobe, collecting duct and gran ular cell types. Obviously, further histogenetic
or cytogenetic studies will be necessary to elucidate the
clinicopathological significance of these findings and whether
they result in different behavior among these types of renal cell
carcinoma.
In conclusion, clear cell renal cell carcinoma of alveolar
architecture expressed high ' attenuation on early enhanced
dynamic CT scanning, whereas those of acinar architecture
showed iso-attenuation with the renal medulla . The papillary,
granular, collecting duct and chromophobe cell types showed
iso-attenuation on early enhanced dynami c CT scanning. Expression of high attenuation on early enhanced dynamic CT
scanning seems to be an important clue that a renal cell carcinoma
is a clear cell tumor of alveolar architecture.
Acknowledgment
This study was supported by the second term Comprehensive 10
Year Strategy for Cancer Control of the Health and Welfare
Ministry of Japan .
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