Article Type : Research Article
Authors : Iosefi DY, Vinidchenko MA, Demchenko NS
Keywords : Magnetic resonance spectroscopy; Renal cell carcinoma; Kidney cancer
The article provides an experience in the use of
morphometric signs in the differential diagnosis of renal cell carcinoma with
magnetic resonance imaging. A significant restriction of diffusion in renal
cell carcinoma and the presence of a relatively large extra renal component can
be used as additional criteria in the differential diagnosis of kidney cancer.
The kidney cancer
remains in focus of continuous attention of researchers and clinicians on the
problem of magnetic resonance imaging in oncourology. This is due to an
increase in morbidity with an annual growth rate of 6-10% and suboptimal
relapse-free survival of patients after treatment [1]. Renal cell carcinoma is
a heterogeneous group of tumours. Renal cell carcinoma is most often diagnosed
as an accidental finding on MRI. Currently, among urological tumors, kidney
cancer ranks third after neoplasms of the prostate and bladder, and in terms of
mortality is in the first place. In the world, approximately 250 thousand and
100 thousand people, respectively, get sick and die from kidney cell cancer
every year [4-8]. In 2014, 22,234 new cases of kidney cancer were detected in
Russia, of which 45.3% were women and 54.7 % were men. In the structure of
cancer incidence in women, this was 3.3 %, which corresponds to the 12th place
in the frequency of occurrence, in men-4.7 % and 9th place, respectively [1].
The "rough" indicator of the incidence of RP per 100 thousand male
population in 2014 was 17.96. For the period 2004-2014, this indicator
increased by 38.3 %. The standardized indicator of the incidence of RP per 100
thousand male population of Russia was 13.13.This indicator increased by 24.3%
over a 10-year period [1]. The traditional position of oncologists is based on
the fact that for a differentiated diagnosis of kidney cancer with a systemic
process, solid tumor metastases and abscesses, a histological examination of
the tumour is required, even in cases where the diagnosis seems clear [2]. At
the same time, accurate non-invasive diagnosis of large kidney tumors at an
early stage is still an urgent task, including for optimizing the biopsy point.
The most frequently detected asymptomatic, randomly visualized with radiation
methods of investigation, small tissue formations with an unidentified
histology structure are grouped into the cohort of kidney incidents or
"radiologists tumor". The diagnostic limitations associated with
percutaneous biopsy, possible complications of the biopsy (bleeding, urinary
fistulas, exacerbation of chronic pyelonephritis), the risk of dissemination of
tumor cells along the biopsy channel and the development of implantation metastases,
the probability of receiving a false-negative response, once again emphasize
the value of accurate characterization of kidney formations by MR imaging. MRI
is a decisive argument for examination in the case of local tumor spread,
determining its invasion into neighboring anatomical structures, the presence
of suspected tumor thrombus in the renal vein or inferior vena cava. It also is
extremely useful in cases where the use of X-ray computed tomography (CT) is
impossible due to an allergic reaction to a contrast agent, kidney failure [3]
or ambiguous results of an already performed CT.
In this regard, the
role of imaging, and first of all, magnetic resonance imaging (MRI), as an
alternative to X-ray methods of investigation, increases in the algorithm of
research in cases of suspected malignant kidney tumors.
In general, MRI is
comparable to CT in detecting kidney formations: the sensitivity of the method
is 93.5 % compared to 93.8% in CT [5]. The complete accuracy of MRI in the
differential diagnosis of renal formations was superior to that of CT. It is
known that MRI data on the size and localization of the neoplasm, the type of
its growth, the presence and preservation of the pseudo-capsule, the fibrous
capsule of the kidney anterenal and retrorenal fascia, the severity and nature
of secondary changes in the tumor tissue are comparable with the results of
path morphological examination of the removed tumor, which allows the
radiologist to make a reasonable assumption about the benign or malignant neoplastic
process. Pulse sequences with suppression of the signal from fat help to
distinguish fat-containing kidney tumors (lipoma, angiomyolipoma, fibrosarcoma)
from renal cell carcinoma, detect cysts and tumors smaller than 1 cm [5]. It is
believed that the data on the prevalence of kidney tumors obtained during MRI
are more informative than similar CT data and help to more reliably determine
the T-and N-stages of the malignant process. It was shown that the T-stage was
reliably determined by CT in 78.4 % and MRI in 84 % of cases, and the N-stage
in 81.8 and 79.5%, respectively. MRI, in contrast to CT, is highly informative
in detecting the pseudocapsule of a kidney tumor, which is most often
characterized by highly or moderately differentiated kidney formations up to 4
cm in size [5]. Among kidney cancers in adults, renal cell carcinoma occurs in
90-95 % of cases, and light cell carcinoma accounts for 70-75 % of all cases of
renal cell carcinoma, thus being the main object for research.
One of the directions of
modern oncourology is the identification of factors that allow non-invasively
obtaining information about the malignant nature of the process. For example, a
non-invasive diagnosis of renal cell carcinoma is difficult, given the
coincidence in appearance with epithelioid angiomyolipoma containing a small
amount of fat and oncocytoma. Despite
the fact that angiomyolipomas are usually clearly delineated and grow
expansively, pushing and squeezing the surrounding tissues, there are cases of
invasive growth, both in the direction of the pelvis, and extrarenally with the
germination of the renal capsule and infiltration of the perinephral tissue.
Blood vessel invasion and metastasis were not observed in typical
angiomyolipoma. Observations of renal sarcoma on the background of
angiomyolipoma are rare [7]. The examination often reveals a picture of
retroperitoneal hematoma caused by spontaneous rupture of the angiomyolipoma
Along with the classic angiomyolipoma, consisting of 3 components and
designated as a benign tumor, the WHO histological classification provides for
the isolation of a potentially malignant mesenchymal tumor, called epithelioid
angiomyolipoma. Epithelioid angiomyolipoma is characterized by a predominant
proliferation of epithelioid cells and a small amount of adipose tissue [6].
Due to the relatively low fat content, epithelioid angiomyolipomas are often
visualized as renal cell carcinoma when using radiation diagnostic methods. The
tumor may have foci of necrosis, may spread to extrarenal tissues, renal and
inferior vena cava. Epithelioid angiomyolipoma is capable of metastasis to the
lymph nodes, liver, and lungs [5-8]. The morphometry of the kidney tumor
process is determined by the ratio of the expansive and infiltrative
components. The microenvironment of tumor cells is characterized by such
factors as interstitial blood flow, oxygen concentration, acidity, osmolarity,
and oncotic pressure of interstitial fluid. The metabolic and
cellular-molecular aspects of the microenvironment, being closely interrelated,
can significantly affect the properties of the neoplasm-heterogeneity,
invasiveness, metastatic potential and tumor progression [5-7].
Factors of the stromal
microenvironment include: endothelial cells, pericytes, smooth muscle cells, fibroblasts,
myofibroblasts, extracellular molecules (adhesion molecules, growth factors,
hormones, proteases and other enzymes, metabolites, extracellular matrix,
collagen, elastic and argyrophil fibers, as well as nerves. The extracellular
matrix determines the structure of the tumor. The presence of an infiltrative
component of tumor growth leads to the presence of an irregular shape and
violation of the anatomical structure due to its replacement, against the
background of compression due to the volumetric effect. The shape of the tumor
is determined by the localization of the source of its growth, its relationship
with the microenvironment and the presence of anatomical barriers (capsules,
fascia, and bone structures). One of the signs of a tumor is a deformation of
the border of the parenchyma and sinus structures, which allows us to assume
the presence of a focal lesion. Deformity, change in structure, or infiltration
of the kidney capsule also allows you to clarify the nature of the process. The
combination of deformation and infiltration leads to morphometric changes, and
on the basis of empirical data, a hypothesis is formed about an independent
sign of malignancy – the value of the cortical-tumoral angle of more than 90?.
The method of differential diagnosis, according to MRI data with tumor
morphometry, allows you to get a reliable result in the diagnosis of kidney
cancer without lengthening the scan time and description.
The aim of this study
was to improve the MR-diagnosis of renal cell carcinoma based on
MR-morphometric and diffusion parameters, taking into account the
microenvironment of tumor cells.
To determine the
differential diagnostic morphometric and diffusion parameters based on the
results of MRI in the diagnosis of renal cell carcinoma.
The material for the
study was tomographic data of 20 patients with renal cell carcinoma, 10
patients with angiomyolipomas and 10 patients with simple intraparenchymal
kidney cysts.
The
algorithm we used included
Protocol of retroperitoneal MRI Visualization in
T2, T2fs, T1 FS, DWI, embedded axial, sagittal, and coronal planes. Detailed
characteristics of MRI semiotics of kidney formations, including MRI signs of
individual structural elements and path morphological examination. The
cortical-tumoral angle was measured using a T2-weighted sequence in the axial
and coronal planes. The series were laid through the cup-pelvic system and the
area of the kidney gate to obtain the maximum cross-sectional area of the
kidney parenchyma and its pelvis. The top of the cortical-tumoral angle was set
at the border of the pelvis and the renal pyramid closest to the tumor, and its
sides were laid tangentially to the tumor borders. The ADC in the tumor was
measured by DWI (b0-b1000) using the small areas of change method. Diffusion
parameters were measured in the solid and cavity components of the tumor, the
parenchyma of the cerebral and cortical layers of the kidney. We calculated the
value of the measured diffusion coefficient, apparent diffusion coefficient (ADC),
which is determined by the formula: ADC = -In (S/S0) /b, where: S0, S is the
intensity of the MP signal without and under the action of diffusion gradients,
b is the diffusion factor. Statistical data processing was carried out using
Microsoft Excel programs. The reliability of differences in the frequency of
detection of the trait was evaluated using the Student's criterion. The
differences were considered significant at p < 0.05. The material for path
morphological examination was obtained after biopsy, various types of surgical
intervention and autopsy. The reliability of the MRI data was evaluated
directly during the operation or familiarized with its protocol.
According to MRI data, tumor processes in the kidney were visualized and described, the exact size of the formations was determined, and the local spread and invasion of tumors into neighboring anatomical structures were studied. As a result of the study, it was found that the average diameter of the malignant tumor was 3.2 cm (from 2.6 to 11.5 cm). The average volume of the tumor was 19 cm3. Tumors were more often located in the middle segment of the kidney, and more than one segment was involved in 12 (60 %) patients. The tumor tissue involved the kidney capsule in 15 (75%) patients, the spread to the pelvis was detected in 7 (35%) cases, and the vessels of the renal pedicle were involved in 3 (15%) cases.
Table 1: The value of the cortical-humoral angle depending on the prevalence of education.
T-criterion
for TNM |
?1 |
?2 |
?3 |
?4 |
AML |
Simple
intraparenchymal cysts | ||||||
a (less than 4 cm) |
b (4-7
cm) |
Less
than 4 cm |
4-7
cm |
Less
than 4 cm |
4-7
cm | |||||||
a |
b |
c | ||||||||||
9 |
5 |
4 |
- |
1 |
- |
1 |
7 |
3 |
6 |
4 | ||
The average value of the
cortical-tumoral angle in the axial projection |
111 |
117 |
121 |
- |
127 |
- |
155 |
43 |
73 |
62 |
77 | |
The average value of the
cortical-tumoral angle in the coronal projection |
123
|
109
|
132
|
- |
135 |
- |
147 |
50
|
81
|
59
|
75
|
In the group with angiomyolipomas, the average diameter of the formation was 2.7 cm (from 0.9 to 3.6 cm). The average volume of the tumor was 10 cm3. Tumors were more often located in the lower segment of the kidney, and more than one segment was involved in 3 (30%) patients. Among patients with simple intraparenchymal kidney cysts, the average diameter of the formation was 3.5 cm (from 1.1 to 5.2 cm). The average volume of the tumor was 22 cm3. Tumors were more often located in the lower segment of the kidney, and more than one segment was involved in 3 (30%) patients. The value of the cortical-tumoral angle was different depending on the prevalence of the tumor, the results are presented in Table 1. The prevalence of renal cell carcinoma was estimated taking into account the TNM classification (2002) and the R. E. N. A. L. classification. The nephrometric score system R. E. N. A. L. (R. E. N. A. L. scale) is used to predict the complexity of performing kidney resection and predict possible complications after performing kidney resection (Table 1).
From the results of the measurements shown in Table 1, it follows that the average value of the cortical-tumoral angle (including all measurements in axial and coronal projections) for renal cell carcinoma is 120?. The average value of the cortical-tumoral angle for angiomyolipomas is 56?, for cysts it is 67?. According to the Student's criterion, the difference between the obtained values of the cortical-tumoral angle for renal cell carcinoma and benign processes is significant at p=0.001(TEM = 18.9) for angiomyolipomas and p=0.001 (TEM = 19.1) for cysts (Table 2).
Table 2: ADC values depending on the staging criteria for T.
T-criterion
for TNM |
?1 |
?2 |
?3 |
?4 |
Other
conditions | |||||
a
(less than 4 cm) |
b(4-7
cm) | |||||||||
a |
b |
c |
Simple
intraparenchymal cysts |
AML | ||||||
The value of the ADC from the solid component of the tumor |
0,00073mm2/s |
0,00077 mm2/s |
0,00072 mm2/s |
- |
0,00085 mm2/s |
- |
0,00083 mm2/s |
0,0033 mm2/s |
0,00173 mm2/s | |
The value of the ADC value
from the medullary layer of the kidney along the periphery of the tumor |
0,00165 mm2/s |
0,00175 mm2/s |
0,00167 mm2/s |
|
0,0012 mm2/s |
|
0,00133 mm2/s |
0,00173 mm2/s |
0,00165 mm2/s |
According to analysis of the measurement data in table 2, it shows that the mean ADC value for renal cell cancer in its solid component is 0,00075??2/s/ It is significantly below the calculated values of the diffusion coefficient for the renal parenchyma 0,0016??2/s, the contents of the cyst 0,0033??2/s (p=0.001 t = 45.7), and angiomyolipoma 0,00165??2/s (p=0.001 t = 32.8). Appraisal values for R. E. N. A. L. and cortico-tumoural the angle of the operated patients are presented (Table 3).
Table 3: RENAL score values and cortical-tumoral angle.
R.E.N.A.L. |
The average value of the cortical-tumoral angle |
Number of observations | |
Axial projection |
Coronal projection | ||
4-6 |
113 |
118 |
14 |
7-9 |
122 |
133 |
5 |
10-12 |
155 |
147 |
1 |
Table 4: Ratio of extrarenal and intraparenchymal components.
T-criterion
for TNM |
?1 |
?2 n=4
|
?3 |
?4 n=1 |
Other
conditions | |||||
a
(less than 4 cm) n=9 |
b (4-7
cm) n=5 | |||||||||
a |
B n=1 |
c |
Simple
intraparenchymal cysts n=10 |
AML n=10 | ||||||
Ratio of extrarenal and
intraparenchymal components |
0,23 |
0,35 |
0,42 |
- |
0,62 |
- |
0,76 |
0,11 |
0,14 |
From the obtained data
(Table 3), it is assumed that a more obtuse cortical-tumoral angle corresponds
to higher values on the R. E. N. A. L scale, but the small size of examined
group does not allow us to consider the observational data statistically reliable.
The results of the measurement of the extra renal and intraparenchymal
components, measured by the formula h (height of the formation component above
the parenchymal boundary)/H (height of the formation component below the
parenchymal boundary) are presented (Table 4).
The average value of
the ratio of extra renal and intraparenchymal components in the group of
observations of renal cell carcinoma is 0.34, for simple mainly
intraparenchymal cysts 0.11, and for typical angiomyolipids 0.14.
According to the Student's criterion, the difference between the obtained values of the ratio of extra renal and intraparenchymatous components for renal cell carcinoma and benign processes was significant at p=0.001 (TEM = 3.9) compared with angiomyolipomas and p=0.001 (TEM = 4.6) compared with cysts. Typical observations of renal cell carcinoma, angiomyolipoma, and simple kidney cyst with measurement examples (Figure 1).
Figure 1: MR picture of angiomyolipoma of the right kidney typical and epithelioid with hemorrhagic impregnation.
In the posterior lip of
the lower segment of the right kidney, a solid structure of the formation was
revealed, measuring 35 x 34 x 38 mm. Along the contours of the formation in the
sinus and pararenal tissue, areas of fat structure, with dimensions of at least
56 x 59mm. Pronounced edema of the paranephral fiber, areas of hemorrhagic
impregnation in the tumor and posterior to the kidney (the process is limited
to the Gerot fascia), epithelioid angiomyolipoma with signs of infiltrative
growth, with the presence of restriction of diffusion ADC 0.000925-0.0014 mm2/s.
In the lateral parts of the upper segment of the right kidney, a formation with
extrarenal growth and the presence of fat in the structure, measuring 24 x 26 x
37 mm, a typical angiomyolipoma, restricts the diffusion of ADC
0.001052-0.001628mm2/s (Figure 2).
Figure 2: MR-picture of renal cell carcinoma.
Thus, the data obtained
indicate that the observed cortical-tumoral angle for renal cell carcinoma is
at least 90 degrees and the obtuse angle is characteristic of infiltrative
growth in a malignant tumor. A significant restriction of diffusion in renal
cell carcinoma and the presence of a relatively large extra renal component can
be used as additional criteria in the differential diagnosis of kidney cancer.
The authors declare no
conflicts of interest.