# Histological Characterisation of Small Renal Masses and Incidence of Silent Renal Masses

Authors: Sergio Almenar Medina; Ana Calatrava  Fons
Journal: Advances in Urology
 (2008)

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## Abstract

With the introduction of sonographic and CT examinations, the number of small renal masses detected has increased. Benign neoplastic lesions are usually smaller than 4 cm
in size, whilst the most common types of renal cell carcinomas have a mean size greater than that, but we must not forget that a significant number of small masses are renal cell carcinomas; even though the rate of benign cases increases as the diameter of the lesions decreases, therefore, size itself cannot be used to rule out a diagnostic of malignancy and often image characteristics are not enough to predict the nature of the lesion with certainty. In this case, histological confirmation must be recommended. Ideally, the histological study must be conducted on the surgical specimen, even though biopsy can be an option in selected cases.


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## Body

## 1. Introduction

Since  the beginning of the eighties, with the
introduction of sonographic and CT examinations, the  number of small renal
masses detected is greater than it was previously, when they were discovered by
clinical methods [1]. According to a study conducted by The New York University
Medical Center, the number of renal masses smaller than 3cm which were
detected in a period of 5 years during the eighties was five times greater than
that found in a similar period during the seventies [2] due to, according to
Bosniak, the increase in the number of abdominal image studies carried out and
to the systematic inclusion of kidneys in these studies. In the Wunderlich
series [3], the percentage of tumours of less than  4cm increased from 28% in 1985
to 61% in 1995.These lesions can be sporadic or associated to
hereditary syndromes, chronic  renal failure, or renal transplantation. In the
first case, they can be detected during the course of abdominal studies due to
renal  symptoms or other causes.
In the second case, they are detected during the illnesses’ follow-up or as a
consequence of specific screening programmes.In every case, masses can be solitary or multiple and
may be solid, cystic, or solid-cystic. Depending on their cystic component in
images, they can be classified into four categories. Lesions belonging to Bosniak
I y II are benign, whereas 59% of Bosniak III and 100% of Bosniak IV are
malignant [4].


## 2. Cystic Renal Lesions

Renal cysts are frequent lesions of variable size,
which appear associated to different clinical situations. Histologically, they
are lined by a single layer of cells which may be cubical in the beginning but
become more or less flattened as the cyst increases in size. However, sometimes
this epithelium may develop hyperplastic lesions, giving way to the big
discussion that exists about possible malignant transformation.Simple renal cysts, whether solitary or multiple, are
very variable in size but are frequently smaller than 4 cm. Usually, they are
autopsy incidental findings and have no clinical relevance.In polycystic kidney disease (dominant or recessive),
cysts have a cuboidal or flattened lining which may proliferate to form
papillary structures inside.In acquired renal cystic  disease, which is associated to dialysis, the
majority of the cysts measure between 0.5 and 2 cm, but may develop renal cell
carcinomas mainly of papillary type. The risk of developing a carcinoma in
patients which are undergoing dialysis is greater in those who have  developed  acquired renal
cystic  disease  [5].


## 3. Solid and Complex Renal Masses

Solid and complex renal masses are mainly of
neoplastic origin but some  inflammatory
lesions may also have equivocal sonographic images, as it may be seen in
Lebret’s series, where 22 out of 106 studied lesions turned out to be  inflammatory  tissues,
abscesses, or granulomatous pyelonephritis [6]. On the other hand, most renal
cell carcinomas are solid, but 40% of them have a cystic component [7].Some of the benign neoplastic lesions are usually
smaller than4cm in size, but we must not forget that, to reach its final size, every lesion
must go through this initial stage. Therefore, size itself is not a  criterion which can be
used to rule out a diagnostic of malignancy.The most frequently detected benign neoplasms are
oncocytomas and angiomyolipomas.Papillary adenomas are tumours with papillary or
tubular architecture of low nuclear grade and 5 mm in diameter or smaller [8].
These are the most common neoplasms of the epithelium of the renal tubules and
have been found in 40% of autopsies of patients older than 70 years. Most papillary
adenomas are silent, solitary, and occur just below the renal capsule.
Histologically, they have tubular, papillary, or tubulopapillary architectures
corresponding closely to types 1 and 2 of papillary renal cell carcinoma. Loss
of the Y chromosome and a combined trisomy of chromosomes 7 and 17 are the
first genetic alterations we can find in papillary tumours and the sole
karyotype change in papillary tumours from 2 mm to 5 mm in diameter, all with
nuclear grade 1. However, it is not possible to distinguish adenomas and
carcinomas by genetic changes, because many carcinomas show only a few genetic
alterations [9]. Therefore, the difference between low-grade papillary renal
cell carcinoma and adenoma depends mainly on size [8].Metanephric adenoma is another solid, less frequent, typically
benign renal tumour, which ranges widely in size. Jones et al. have reported 7
incidental cases, all of them are less than1cm, although symptomatic cases are
usually larger than
3cm
[10].The most common types of renal cell carcinomas have a
mean size which is greater than4cm,  but some unusual types have a mean size of less
than 4cm. According to Nassir, the mean size of multilocular cystic renal cell carcinoma
is  3.4cm  [11] and the acquired cystic disease-associated RCC usually has a mean size of
around 3cm and shows peculiar morphological and immunohistochemical features [12, 13].
Normally, they have a microcystic architecture and Fuhrman grade 3. They also
describe another group which they refer to as “clear-cell papillary RCC of the
end-stage kidneys.”Papillary renal tumours with oncocytic cells of the
adult have, according to Lefevre, a mean size of3.3cm,  they are intrarenal, with sharp edges and all,
except one, have Fuhrman grade 2 [14].Carcinomas belonging to the hybrid oncocytic tumour
variety (which frequently occur in the Birt-Hogg-Dubé syndrome) are usually of
a small size and their behaviour is between the oncocytoma and the well-differentiated
chromophobe renal cell carcinoma [15].Finally, 10 out of the 13 tubulocystic renal cell
carcinomas described by Yang et al. [16] measured less than  3cm.


## 4. Relationship between Tumoural Size and Histological Type

One of the main problems when it comes to analysing
this relationship is that most of the small renal tumour series are based on
clinical and radiological data but histological confirmation lacks [27], especially
when lesions are diagnosed incidentally, because the biopsy is not indicated as
a routine method [19, 22, 28]. Moreover, the series which includes a
histological study uses different criteria to indicate surgery or biopsy,
different cutoff points for small masses, and even different pathologic
classifications, which make
it even more complicated to draw general conclusions (Table 1) [5, 6, 17–25].Table 1
Small renal masses with histological
confirmation.N: total number of cases; n: number of cases; RCC: renal cell
carcinoma; OM: other malignant tumors; Onc: oncocytoma; AML: angiomyolipoma;
AP: papillary adenoma; OB: other benign lesions.
SizeNRCCOMOncAMLAPOBn%n%n%n%n%n%Kunkle,
2007 [17]Median2cm423788.100.049.500.000.012.4Lebret,
2007 [6]Median3cm1355540.7139.61511.142.900.04835.6Chawla,
2006 [18]Most<4cm211780.900.0419.100.000.000.0Vasudevan,
2006 [19]All<5cm704158.668.61420.0912.900.000.0Neuzillet,
2005 [5]Mean3.7cm151280.000.016.700.016.716.7Mindrup,
2005 [20]Mean1.7cm732838.622.711.445.52230.11621.9Volpe,
2004 [21]All<4cm9888.900.0111.100.000.000.0Wehle,
2004 [22]All<4cm5480.000.0120.000.000.000.0Frank,
2003 [23]All<4cm2935255987.200.02749.3672.3160.5190.7Bosniak,
1995 [24]All<3.5cm262284.600.0415.400.000.000.0Silverman,
1994 [25]All<3cm352777.125.700.012.900.0514.3Nevertheless, it is clear that a significant number of
small solid and complex masses are renal cell carcinomas and they are, according
to some authors, more frequent than benign lesions [23, 26], even though the rate of benign
cases increases as the diameter of the lesions decreases.In these cases, it is not possible to predict the
behaviour that the lesions will have later neither by their image
characteristics [29] nor by their growing speed throughout a short period of
time, due to the fact that this speed is not related to the tumoural volume or
to the histological grade at a given time [18, 30]. This speed may vary throughout
time for a same tumour [31] and can be temporarily zero, even though it is a
carcinoma [22]. According to Kunkle, there are no any significant differences
between tumours with growth zero during a period of one year and those which
have positive growth during the same period at the time of the diagnosis. In
both cases, the mean size is of 2cm and 80% of the lesions of growth zero happened
to be carcinomas [17].According to a recent study by Tabibi [32], amongst
renal cell carcinomas, there is no significant relationship between size and
histological subtype, even though it is true that, in long series, the size of
tumours of the same type tends to gather around a certain value. The usual
histological subtypes of renal cell carcinoma have a mean size of more than 4cm [33] and the same happens with translocation Xp11 renal cell
carcinomas [34] and with translocation t(6;11)(p21;q12) [35], where the mean
diameter is 6.8 cm and 6.28 cm, respectively. When carcinomas are analysed
according to size, it can be observed that when the mean tumoural diameter
increases, the ratio of papillary carcinomas decreases and that of chromophobe
carcinomas increases (Table 2) [20, 23, 26].Table 2
Distribution of histological subtypes
of renal cell carcinoma depending on size. RCC: renal cell carcinoma;N:
total number of RCC; n: number of each subtype; RCCcc: clear cell RCC; RCCp:
papillar RCC; RCCchr: chromophobe RCC.
RCCRCCccRCCpRCCchrNn%N%n%Schlomer, 2006 [26]0-1cm6583,300,0116,71-2cm382565,81026,337,92-3cm634977,81219,023,23-4cm524382,3917,300,04-5cm282278,6414,313,6>5cm1028184,41111,544,1Mindrup, 2005 [20]Media1,7cm28735,01168,800,0Media4,7cm401365,0531,23100,0Frank, 2003 [23]0-1cm25,674,40,01-2cm59,938,61,52-3cm70,226,03,83-4cm80,224,53,8


## 5. Relationship between Size and Aggressiveness of Renal Cell Carcinomas

It cannot be categorically assured that the size of a
tumour is directly related to its histological grade and its clinical
aggressiveness. For example, low-grade tubular-mucinous renal neoplasia (also
known as mucinous tubular and spindle cell carcinoma) is a neoplasia with a low
grade of aggressiveness and, nevertheless, usually has a mean diameter which is
larger than 4 cm [12, 41, 42]. In addition, chromophobe carcinomas are usually
larger but less aggressive than clear cell renal cell carcinomas [33]. In the
same way, among small renal cell carcinomas, the clear cell subtype is much
more frequent than
chromophobe carcinoma (Table 3) [5, 6, 17–20, 23, 25, 26, 31, 36, 37, 38].Table 3
Percentage of histological subtypes
of renal cell carcinoma in small renal masses. RCCcc: clear cell
renal cell carcinoma; RCCp: papillary renal cell carcinoma; RCCchr: chromophobe renal cell carcinoma; RCCo:
other variants of renal cell carcinoma.
SizeRCCccRCCpRCCchrRCCon%N%n%n%Kunkle,
2007 [17]Median2cm2464,91232,400,012,7Lebret,
2007 [6]Median3cm4174,51018,247,300,0Chawla,
2006 [18]Most<4cm952,9741,200,015,9Pankhurst,
2006 [36]21
of them<1mm28,02288,000,014,0Schlomer,
2006 [26]Only<4cm12276,73119,563,800,0Vasudevan,
2006 [19]All<5cm3278,049,8512,200,0Neuzillet,
2005 [5]Mean37mm758,3325,0216,700,0Mindrup,
2005 [20]Mean17mm725,01139,300,01035,7Kato,
2004 [31]All<4cm1583,3316,700,000,0Frank,
2003 [23]All<4cm197077,043617,01254,9281,1Shishikura,1996
[37]All<2,5cm8486,633,100,01010,3Silverman,
1994 [25]All<3cm1763,0311,1311,1414,8Yamashita,
1992 [38]All<3cm2672,200,0719,438,3Amongst small size tumours, there is a higher rate of
low-grade lesions and this percentage tends to decrease as the tumoural size
increases (Table4) [23, 26, 39], but we must not forget that among carcinomas
which are smaller than 4 cm, there is a significant ratio, between 6% and 50%, of high-grade tumours (Table 5) [5, 6, 18, 20, 21, 23, 25, 39, 40].Table 4
Percentage of low-grade and high-grade
carcinomas depending on size. LG: low grade; HG: high grade.
Schlomer, 2006 [26]Hsu, 2004 [39]Frank, 2003 [23]LG %HG %LG %HG %LG %HG %0-1cm83,316,7——90,99,11-2cm94,75,3——88,611,42-3/<3cm71,428,672,028,093,66,53-4cm71,128,9——81,318,74-5/3–5cm67,932,167,832,277,622,45-6cm53,846,2——69,330,76-7/>5cm44,455,640,459,660,939,1>7cm36,263,8——37,962,1Table 5
Distribution of Fuhrman grades in
renal cell carcinomas. F1, F2, F3, F4: Furhman grades.
SizeRCCF1+F2F3+F4nn%n%Lebret,
2007 [6]Median3cm575189,5610,5Chawla,
2006 [18]Most<4cm171694,115,9Neuzillet,
2005 [5]Mean37mm12650,0650,0Mindrup,
2005 [20]Only<4cm15912377,43622,6Peces,
2004 [40]Only<4cm121191,718,3Hsu,
2004 [39]Only<3cm503672,01428,0Volpe,
2004 [21]All<4cm8450,0450,0Frank,
2003 [23]Only<4cm48042087,56012,5Silverman,
1994 [25]All<3cm272488,9311,1In Schlomer’s series [26], 16.7% of the tumours which
are smaller than 1cm are high-grade tumours and 38% of the 50 carcinomas with a size equal to or
less than 3cm included in Hsu’s series [39] extend beyond the renal capsule.This last series also shows that there is no
significant difference in grade or stage between tumours of less than3cm and those
of 3 to 5cm,
but these differences do exist between tumours of less than  5cm and those
which are greater. In the results reported by Tabibi [32], extracapsular spread
is rare in tumours of less than 4cm, but he does not find statistically significant
differences in grade when the cutoff point is established at 4 cm. Schlomer and
Miyagawa’s results [26, 43] point towards this same direction. This is why some
authors question that the cutoff point is established at 4 and not at 5 cm
[39, 43].


## 6. Incidental Renal Tumours

Most of the incidentally diagnosed lesions are benign.
In a classical series which studied 205 incidental lesions of less than1cm found in
autopsies, the most common was medullary fibrous nodules (159), followed by
cortical adenoma (49), leiomyoma (12), lipoma (7), and myolipoma (13) [44].Renal carcinomas which are incidentally diagnosed
represent between 15 and 60% of the total number of carcinomas, depending on
the series.A lot of them are smaller than4cm  [28].
Generally speaking, carcinomas discovered incidentally are smaller than those
which are symptomatic [45, 46]. Their mean diameter is 5.7 cm in contrast with the 8.7 cm in
symptomatic cases. Moreover, the mean size has reduced notably thanks to image
techniques. The mean diameter of renal tumours incidentally found in autopsies
at the University of Iowa decreased from 4.63 cm in the fifties to 1.65 cm in
the nineties [20]. They are also associated with a lower stage and a lower
nuclear grade [47], as well as with the increasing age of patients [48].Therefore, it would be reasonable to consider
incidental carcinomas as a group with its own clinical and pathological
significance, even though we cannot establish at present whether they are
discovered incidentally because they still small or because they have their own
particular biological characteristics which make them behave in a less-aggressive
way.On the other hand, the presence of certain syndromes
may influence the size that some tumours reach, as it happens to
angiomyolipomas which have a greater mean diameter in the context of tuberous
sclerosis than when they appear sporadically [49].


## 7. Conclusions

A significant rate of small renal masses,  discovered either
symptomatic or incidentally, are carcinomas. Moreover, up to 50% of carcinomas measuring less than 4 cm are
high-grade lesions and some of them extend beyond the renal capsule despite the
fact that they have got such a small diameter. Therefore, when a small renal
mass is detected, the
size itself is not a reliable feature to rule out a diagnostic of malignancy.
Unfortunately, there are many times when image characteristics or speed of
growth along a period of several months are not enough to predict the nature of
the lesion with certainty. In these cases, histological confirmation must be
recommended.Most of the times, the histological study is conducted
on the surgical specimen, though biopsy can be considered a good option if
surgery represents a high risk for the patient. The problem is that the smaller
a mass is, the more difficult it is to get the right sample; but the bigger it
is, the less representative the whole of the lesion is. That is why there is no
general agreement about biopsy indications at the moment. On the other hand,
surgical resection in the early stage of the tumour is still the best treatment
option for renal cell cancer, and small masses are good candidates for
conservative techniques. From this point of view, surgery implies a double
benefit because it is a good therapeutic choice and provides the most accurate
diagnosis.Risks and benefits must be evaluated in every single case
taking into account the particular clinical situation of the patient as well as
the available technical means and the expertise of the medical team involved.



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