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Pathology of Renal Tumors

Prof R K Gupta

Pathology of Renal Tumors


Prof R K Gupta
Department of Pathology, Sanjay Gandhi PGI, Lucknow-226014
An Over View
Renal neoplasms constitute an important group of tumors both in adults and children accounting for
2.5-3% of all neoplasia in adults and 8-10% of all neoplasms in infants and children. Majority of
renal neoplasms in adults are of epithelial origin and are malignant. Renal cell carcinoma alone
accounts for approximately 2% of all adult cancers, estimated deaths attributable to it being
approximately 100,000 world over every year; India contributes about 5,000 patients dying of renal
cell carcinoma to this pool(1-2). Increasing incidence of renal tumors has been observed over past
two decades, at least in part due to improved diagnostic techniques and early detection.
Classification of Renal Tumors in Adults
Ever since the earliest report of a confirmed renal tumor by Miriel in 1810 (3), increasing number of
renal tumors have been documented. Earlier classification as proposed by Konig (4) was based on
gross morphological features of the tumor and the renal tumors were divided into fungoid,
medullary, scirrhous and steatomatous types. Later, Rayer (5) on the basis of clinical features along
with tumor morphology classified renal neoplasia as latent (encephaloid tumors without renal
enlargement or hematuria)), calaceal (associated with pain and hematuria) and scirrhous (often with
hematuria).

Pierre Francois Olive Rayer (1973-1867)


Between 1831 and 1838, earliest series of
well documented renal tumors was publish by him
Pathology of Renal Tumors
Gaya Prasad Memorial Pathology Symposium
APCON 2005, Indore; 2nd December, 2005

Pathology of Renal Tumors


Prof R K Gupta

Robin (6) and Waldeyer (7) considered that these tumors were derived from renal tubules. Grawitz
(8,9) while recognizing the epithelial nature of renal carcinoma attributed its histogenesis to intrarenal ectopic adrenal rests and coined the term "hypernephroma" for these tumors. In the first half of
the twentieth century Grawitzs theory became increasingly discredited and the debate was finally
resolved when Oberling et al (10) demonstrated through ultrastructural studies that renal carcinomas
were derived from renal tubular epithelium.

Paul Albert Grawitz (1850-1932)


Proposed that Renal cell carcinoma is
derived from intra-renal adrenal
cell rests and coined the term
Hypernephroma

Elexious Thompson Bell (1880-1963)


His work had a major influence on
benign renal neoplasm. He noted that
the tumors less than 3 cm in size rarely
metastasized. The criteria of the size
of the tumor was later incorporated in
several classifications of renal tumors
including that of Mainz 1986.

During past two decades, several classifications for renal tumors have been proposed (Table 1). A
classification of renal adenomas (RCAs) and carcinomas (RCC) introduced by Thoenes et al (11),
popularly known as the Mainz classification of renal cell tumors was based on two morphological
criteria viz. 1) cellular characteristics i.e. the tumor cell types and 2) tissue characteristics i.e. the
growth pattern in general. The malignant tumors were further divided into clear cell, chromophobe,
chromophilic, mixed and spindle shaped/ pleomorphic types (Fig 1). Adenomas were defined as
Pathology of Renal Tumors
Gaya Prasad Memorial Pathology Symposium
APCON 2005, Indore; 2nd December, 2005

Pathology of Renal Tumors


Prof R K Gupta

tumors with grade 1 morphology and upto 1cm in diameter, and were classified into chromophilic,
clear and chromophobe types.
Table 1: Broad classifications of Renal tumors
Classification
Basis
WHO 1981
Morphological basis
Mainz 1986
Cytologic and architectural features
Heidelberg-Rochester Emphasized the importance of molecular genetics
Classification 1997
WHO 1998

Morphological identification of subvariants

WHO 2004

Morphological identification with molecular genetics as secondary


diagnostic criterion

Fig. 1 The basis of Mainz classification of renal tumors


Classification of renal tumors proposed by Heidelberg-Rochester (12) besides, morphological
features also included cytogenetic and molecular characteristics of the tumor.
The WHO 1998 (13) classification of renal tumors failed to acknowledge the advances of the Mainz
and Heidelberg-Rochester classifications (11, 12). In particular granular cell carcinoma, which could
include clear cell, chromophobe and collecting duct carcinoma, was included as a separate
Pathology of Renal Tumors
Gaya Prasad Memorial Pathology Symposium
APCON 2005, Indore; 2nd December, 2005

Pathology of Renal Tumors


Prof R K Gupta

diagnostic category of RCC, as was spindle cell carcinoma which is now recognized as the result of
dedifferentiation in any of the recognized forms of RCC.
The short comings of WHO 1998 (13) classification were rectified in a subsequent WHO 2004 (14)
classification of renal tumors which also included the types of renal cell neoplasia defined by the
Heidelberg-Rochester consensus group (12). Metanephric adenoma was removed from the group of
renal cell tumors and was classified with other tumors of metanephric morphology. Multilocular
clear cell RCC was separated from clear cell RCC because of its benign course, whereas papillary
RCC was divided into two types based on nuclear stratification and cytoplasmic eosinophilia.
Xp11translocation group of tumors and mucinous, tubular and spindle cell carcinoma were
recognized as novel forms of renal cell neoplasia (Table 2).
Table 2: Classification of Renal Tumors in Adults (WHO 2004)
Renal Epithelial Tumors
Non-epithelial tumors
Benign
Benign
Renal oncocytoma
Renomedullary interstitial cell tumor
(medullary fibroma)
Papillary/tubulopapillary adenoma
Angiomyolipoma
Metanephric adenoma
Juxtaglomerular cell tumor
Metanephric adenofibroma
Metanephric stromal tumor
Solitary fibrous tumor
Malignant
Clear cell (conventional) renal cell carcinoma Lipoma
Papillary renal cell carcinoma
Leiomyoma
Chromophobe renal cell carcinoma
Hemangioma
Collecting duct carcinoma
Lymphangioma
Medullary carcinoma
Malignant
Mucinous tubular and spindle cell carcinoma Leiomyosarcoma
Xp11 translocation carcinoma
Rhabdosarcoma
Renal cell carcinoma, unclassified
Synovial sarcoma
Liposarcoma
Tumor of undetermined malignant
Miscellaneous tumors
potential
Multi-locular cystic renal cell carcinoma
Carcinoid tumor
Primitive neuroectodermal tumor
Mixed epithelial and stromal tumors
Mixed epithelial and stromal tumor
Small cell carcinoma
Cystic nephroma
Metastatic tumors
Hematopoeitic tumors
Staging
In 1969, Robson and colleagues (15) published a staging system that was adopted by most clinicians
and pathologists and was shown to correlate well with survival. The TNM classification since its
introduction in 1978 (16) has undergone multiple modifications most recently by American Joint
Committee on Cancer staging of renal cell carcinoma in 2002 (17), which is in practice currently
(Table 3).
Pathology of Renal Tumors
Gaya Prasad Memorial Pathology Symposium
APCON 2005, Indore; 2nd December, 2005

Pathology of Renal Tumors


Prof R K Gupta

Table 3: American Joint Committee on Cancer staging of Renal Cell Carcinoma


(2002)
Stage
Primary Tumor (T)
TX
T0
T1a
T1b
T2
T3a

Characteristics

Primary tumor cannot be assessed


No evidence of primary tumor
Confined to kidney (4.0cm)
Confined to kidney (>4.0 cm and 7.0cm)
Confined to kidney (>7.0 cm)
Tumor directly invades adrenal gland or peri-renal or renal sinus
fat but not beyond Gerota's fascia
T3b
Tumor grossly extends into the renal vein or its segmental
(muscle-containing) branches, or vena cava below the diaphragm
T3c
Tumor grossly extends into vena cava above diaphragm or
invades the wall of the vena cava
T4
Tumor invades beyond Gerota's fascia
Regional Lymph Nodes (N)
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Metastasis in a single regional lymph node
N2
Metastases in more than one regional lymph node
Distant Metastasis (M)
MX
Distant metastasis cannot be assessed
M0
No distant metastasis
M1
Distant metastasis
Tumor, nodes, metastases (TNM) system includes tumors confined within the renal capsule in the
most favorable category. A problem comes with the definition of the renal capsule. We have to
discriminate 4 different structures forming a capsule surrounding a renal neoplasm.
1) The intrarenal pseudocapsule, which is a fibrotic reaction of the peritumoral renal
tissue.
2) The renal capsule, which is the fibrous layer on the outer surface of the kidney. This
structure is absent in the hilar region.
3) The perirenal pseudocapsule, which is a fusion product of the former structures with
the newly built up perirenal fibrosis.
4) Gerota's fascia, which is the fibrous layer covering the perirenal adipose tissue.
Renal cell carcinoma frequently invades the renal venous system and this is the criterion of stage III
A. Invasion must occur in large veins with smooth muscle in their walls and must be at the edge or
outside the main tumor.
Pathology of Renal Tumors
Gaya Prasad Memorial Pathology Symposium
APCON 2005, Indore; 2nd December, 2005

Pathology of Renal Tumors


Prof R K Gupta

Metastasis to regional lymph nodes without distant metastasis occurs in approximately 10%-15% of
cases but more than 50% of patients with enlarged regional lymph nodes have only inflammatory
changes.
Studies have shown that the pathological stage is the most significant prognostic factor for RCC
(17). A 5-year cancer specific survival has been found to be 91-95% for pT1, 74-88% for pT2, 5967% for pT3 and 20-32% for pT4.
Grading
Fuhrmans nuclear grading system (18) is the most popular and clinically useful. It consists of four
grades based on nuclear size and contour, and conspicuousness of nucleoli (Table 4).
Table 4: Histological Grading of Renal Cell Carcinoma
Grade
1
2
3
4

Nuclear features
Round, uniform nuclei approximately 10 in diameter with minute or
absent nucleoli
The nuclei have slightly irregular contours and are approximately 15
in diameter with inconspicuous nucleoli which could be seen at 400x
Moderately to markedly irregular nuclear contours and diameters of
nuclei is approximately 20 with large nucleoli visible at 100x
Nuclei similar to those of grade 3 but also multilobular or multiple
nuclei or bizarre nuclei and heavy clumps of chromatin

Overall, this system finds about 10% of cases to be grade 1, 35% grade 2, 35% grade 3, and 20%
grade 4. Multivariate analyses has revealed that the nuclear grade is an important independent
prognostic factor for RCC. The five year survival rates have been found to be 89-94%, 65-86% and
31-59% for tumor grades 1, 2 and 3/4 respectively.
Immunohistochemistry
The renal cell neoplasms show immunohistological diversity reflecting different histogenesis of
different tumors. Overlapping morphological features of renal tumors sometimes make histologic
subtyping difficult. In these cases cytoarchitectural features along with with immunophenotype and
cytogenetic characteristics may be helpful in accurate diagnosis (Table 5).

Pathology of Renal Tumors


Gaya Prasad Memorial Pathology Symposium
APCON 2005, Indore; 2nd December, 2005

Pathology of Renal Tumors


Prof R K Gupta

Table 5: Immunohistochemical Characteristics of Renal Tumors


D
V
U C
C
Tumor Type
C
E
I
E D
K
K
S
A 3
M
8
1
M
1 4
E
&
9
I
N
1
N
T
8
I
N
Clear Cell RCC
Papillary RCC
Renal Oncocytoma
Chromophobe RCC
Collecting duct carcinoma
Neuroendocrine tumors
Metanephric adenoma
Wilms' tumor
Leomyoma/leiomyosarcoma
Rhabdomyosarcoma
Angiomyolipoma
Lipoma/liposarcoma
Malignant fibrous histiocytoma
Malignant lymphoma

+
+
+
+
+
+
+/+/+/+/+/+/-

+/+/+/+/+
-

+
+
+/+
+
+
+
+
+
+
+

+
+
-

+/+
+/-

+/+
+
+/+
-

A
C
T
I
N

H
M
B
4
5

N
S
E
&
S
1
0
0

C
H
R
O
M
O
G
R

L
C
A

+/+
+
+
-

+
-

+
+/+/+/+
-

+
-

Cytogenetic and Molecular Features of Renal Tumors


The application of molecular and cytogenetic techniques to the study of renal neoplasia has
improved the understanding of the biologic mechanisms responsible for tumorigenesis (Table 6). It
also revealed that several different and specific genetic events are responsible for renal
tumorigenesis which add to correct diagnosis, accurate assessment of prognosis and selecting
appropriate and targeted therapeutic options.

Pathology of Renal Tumors


Gaya Prasad Memorial Pathology Symposium
APCON 2005, Indore; 2nd December, 2005

Pathology of Renal Tumors


Prof R K Gupta

Table 6: Cytogenetic and Molecular Features of Renal Tumors


Clear Cell RCC
Papillary RCC
Chromophobe RCC
Renal oncocytoma
Collecting duct carcinoma
Xp11 translocation carcinoma
Mucinous tubular and
spindle cell carcinoma
AML
Metanephric adenoma

Loss of 3p
Mutations/hypermethylations VHL gene
Trisomies 7 and 17; Loss of chromosome Y
MET mutations in familial and some sporadic cases;
Hypodiploidy
losses of chromosomes 1, Y, 6,10, 13, 17, 21
Losses of chromosomes 1 and Y
t(9;12)(p23;q13), t(5;11)(q35;q13)
Monosomies 1, 6, 14, 15, 22; Loss of heterozygosity 1q
Minimal deletion at 1q32.1-32.2
t(X;1)(p11.2;q21) or t(X;17)(p11.2;q25)
Losses at chromosomes 1, 4q, 6, 8p, 11q, 13, 14, 15;
Gains at chromosomes 11q, 16q, 17, 20q
TSC1 and TSC2 gene inactivation
2p losses
(? Trisomies 7 and 17; ? losses of sex chromosomes)

Renal Tumors in Children


Renal tumors in children constitute about 8% of all pediatric malignancies. Wilms tumor (WT) of
the kidney is by far the commonest renal tumor of childhood (85%). Clear cell sarcoma, rhabdoid
tumor, congenital mesoblastic nephroma, multilocular cystic renal tumor, renal cell carcinoma, and
angiomyolipoma constitute other rarer forms of childhood renal neoplasms (Table 7).
Table 7: Classification of Renal Tumors in Children
Nephroblastic Tumors
Mesenchymal Tumors
Nephroblastoma
Clear cell sarcoma
- Favourable histology
Rhabdoid tumor
- Anaplastic
Congenital mesoblastic nephroma
- Cystic partially differentiated nephroblastoma
Nephrogenic rests and nephroblastomatosis
Metanephric Tumors
Metanephric adenoma
Metanephric adenofibroma
Metanephric stromal tumor

Renal Epithelial Tumors


Papillary renal cell carcinoma
Renal medullary carcinoma
Renal tumors associated with
Xp11.2 translocations
Ossifying renal tumor of infancy

Pathology of Renal Tumors


Gaya Prasad Memorial Pathology Symposium
APCON 2005, Indore; 2nd December, 2005

Pathology of Renal Tumors


Prof R K Gupta

Staging
The key determinant of the staging is the anatomic extent of tumor invasion; therapy is
based on stage and histologic features. Accurate staging is of practical importance since
misstaging can lead to inappropriate therapy
The following table summarizes the North American National Wilms Tumor Study
Group staging system(19) for childhood renal neoplasms (Table 8).
Table 8: Staging for Childhood Renal Neoplasms
Stage

Criteria

I
II
III
IV

Confined to kidney and completely resected


Extends beyond kidney but completely resected
Gross residual tumor, and/or involvement of surgical margins, and/or
tumor in regional nodes (LN metastasis may be microscopic). Local
rupture or spill with contamination of peritoneum.
Hematogenous and distant lymphatic metastases

Bilateral renal tumors

Both in adults and childhood renal neoplasms the pathological evaluation is essential for
1) Histological classification of the tumor
2) Histological grading of malignancy
3) Staging of the tumor

Pathology of Renal Tumors


Gaya Prasad Memorial Pathology Symposium
APCON 2005, Indore; 2nd December, 2005

Pathology of Renal Tumors


Prof R K Gupta

References
1) Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of eighteen
major cancers in 1985. Int J Cancer 1993; 54: 594-606.
2) Cancer incidence, mortality and prevalencd worldwide, version 1.0. IACR Cancer
Base No. 5, Lyon,IARC Press, 2001.
3) Miriel G. Summarized thoughts on the importance of a diagnosis . Paris: 1810.
4) Konig G. Practical treatment of diseases of the kidney as explained by case
histories. Leipzig: C. Cnobloch; 1826.
5) Rayer P. Cancer of the kidney. In: Treatise ondisease of the kidney and the
alteration of urinary secretion. Paris; Book 3:1841, p 675-718.
6) Robin CP. Tretise on eptheliomas of the kidney and the thin granulated filaments
from urinary tubules that are expelled with urine. Gaz dHop Civ et Med 1855;
28: 186-203.
7) Waldeyer W. The development of carcinoma. Arch Pathol Anat Physiol Klin Med
1867; 41: 470-523.
8) Grawitz P. The so-called lipoma of the kidney. Arch Pathol Anat Physiol Klin
Med 1883; 93: 39-63.
9) Grawitz P. The origin of kidney tumors from adrenal gland tissue. Arch Klin Chir
1884; 30:824-34.
10) Oberling C, Riviere M, Haguenan F. Ultrastructure of clear cell epitheliomas of
the kidney (hypernephroma or Grawitz tumor) and its implications for the
histogenesis of the rumors. Bull Cancer Assoc France 1959; 46: 356-358.
11) Thoenes W, Storkel S, Rumplet HJ. Histopathology and classification of renal cell
tumors (adenomas, oncocytoma and carcinomas)The basic cytological and
histopathological elements and their use for disgnosis. Path Res Pract 1986; 181:
125-43.
12) Kovacs G, Akhtar M, Beckwith BJ et al. The Heidelberg classification of renal
cell tumors. J Pathol 1997; 183: 131-133.
13) Mostofi FK, editor. Histological typing of kidney tumors. World Health
Organization, Geneva, (International Histological Classification of Tumours No.
25), 1981.
14) Eble JN, Sauter O, Epstein JI et al, editors. Pathology and genetic of tumors of the
urinary system and male genital organs. World Health Organization Classification
of Tumors. Lyon (France): IARC Press; 2004.
15) Robson CJ, Churchill BM, Anderson W. The results of radical nephrectomy for
renal carcinoma. J Urol 1969; 101: 297-301.
16) Harmer M. TNM classification of malignant tumors. 3rd ed.Geneva (Switzerland):
International Union Against Cancer; 1978.
17) Greene FL, Page DL, Fleming ID et al, editors. AJCCCancer Staging Mannual.
6th ed. New York: Springer-Verlag; 2002.
18) Fahrman SA, Lasky LC, Limas C. Prognostic significance of morphological
parameters in renal cell carcinoma. Am J Surg. Pathol. 1982; 6: 655-663.
19) Beckwith JB. National Wilms tumor study: an update for pathologists. Pediatr
Dev Pathol 1998; 1: 79-84.

Pathology of Renal Tumors


Gaya Prasad Memorial Pathology Symposium
APCON 2005, Indore; 2nd December, 2005

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