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.
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
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
WHO 2004
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
Characteristics
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).
+
+
+
+
+
+
+/+/+/+/+/+/-
+/+/+/+/+
-
+
+
+/+
+
+
+
+
+
+
+
+
+
-
+/+
+/-
+/+
+
+/+
-
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
+/+
+
+
-
+
-
+
+/+/+/+
-
+
-
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)
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
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
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