Recommendations for the reporting of surgically resected specimens of renal cell carcinoma The Association of Directors of Anatomic and Surgical Pathology
A checklist based approach to reporting the relevant pathologic details of renal cell carcinoma resection specimens improves the completeness of the report. Karyotypic evaluation of renal neoplasms has refined but also complicated their classification. The number of diagnostic possibilities has increased and the importance of distinguishing different tumor types has been underscored by dramatic variation in prognosis and the development of targeted therapies for specific subtypes. The increasing number of recognized renal neoplasms has implications for handling renal resection specimens. Furthermore, the prognostic significance of other features of renal neoplasms related to grade and stage has been demonstrated. This guideline for the handling of renal resection specimens will focus on problem areas in the evolving practice of diagnosis, grading, and staging of renal neoplasms. The accompanying checklist will serve to ensure that all necessary details of the renal resection specimen are included in the surgical pathology report.
Recommendations for the reporting of surgically resected
specimens of renal cell carcinoma
The Association of Directors of Anatomic
and Surgical Pathology
John P. Higgins MD
, Jesse K. McKenney MD, James D. Brooks MD,
Pedram Argani MD, Jonathan I. Epstein MD
Department of Pathology, Stanford University, Stanford, CA 94025, USA
Department of Urology, Stanford University, Stanford, CA 94025, USA
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
Received 28 November 2008; accepted 11 December 2008
Summary A checklist based approach to reporting the relevant pathologic details of renal cell
carcinoma resection specimens improves the completeness of the report. Karyotypic evaluation of renal
neoplasms has refined but also complicated their classification. The number of diagnostic possibilities
has increased and the importance of distinguishing different tumor types has been underscored by
dramatic variation in prognosis and the development of targeted therapies for specific subtypes. The
increasing number of recognized renal neoplasms has implications for handling renal resection
specimens. Furthermore, the prognostic significance of other features of renal neoplasms related to
grade and stage has been demonstrated. This guideline for the handling of renal resection specimens will
focus on problem areas in the evolving practice of diagnosis, grading, and staging of renal neoplasms.
The accompanying checklist will serve to ensure that all necessary details of the renal resection
specimen are included in the surgical pathology report.
© 2009 Elsevier Inc. All rights reserved.
1. Scope of the guidelines
The reporting of renal cell carcinoma is facilitated by the
provision of a checklist to insure that pathologists provide all
of the essential information to enable clinicians to optimize
patient care. Classification of renal tumors is complicated by
the wide range of morphological types of ren al cell
carcinoma, some of which have recognized subtypes.
Cytogenetic data have clarified the morphologic features of
some of these tumors, but such data are not routinely
available to assist most practicing pathologists attempting to
classify individual tumors. Nevertheless, consideration
should be given to cytogenetic evaluation for renal cortical
tumors in young patients or tumors of unusual morphologic
appearance regardless of the age of the patient. It is also
important to note that although the biologic aggressiveness
differs for the different types of renal cell carcinoma, staging
and grading of renal cell carcinoma is driven by the behavior
Corresponding author. Department of Pathology, Stanford University,
Stanford, CA 94025, USA.
E-mail address: email@example.com (J. P. Higgins).
0046-8177/$ – see front matter © 2009 Elsevier Inc. All rights reserved.
Human Pathology (2009) 40, 456–463
of clear cell carcinoma, the overwhelmingly most common
subtype. Several aspects of renal cell carcinoma classifica-
tion remain problematic. In spite of the large and growing
number of renal cell carcinoma subtypes, classification of
well-differentiated, low-grade tumors is relatively routine.
However, with increasing tumor grade, the features by which
renal cell carcinomas are classified may be lost or are at least
obscured. Subclassifications of papillary renal cell carci-
noma have been proposed but do not clearly have prognostic
relevance independent of nuclear grade . The grading
scheme proposed by Fuhrman  and modifications thereof
are used to grade clear cell renal carcinomas, but this scheme
was developed before many renal cell carcinoma subtypes
were recognized and may not be applica ble to other
subtypes. Difficulties also arise with respect to the stage of
a renal carcinoma. In particular, it is difficult to assess the
point at which a carcinoma has extended beyond the kidney.
Based on the most current data, this guideline will attempt to
address these problematic points and suggest reasonable
means of providing the information called for in the
Features the association recommends for inclusion in the
final report are selected based on the fact that they are
generally accepted as being of prognostic importance,
required for therapy, and/or traditionally expected (Appen-
dix). The guidelines adhere to the recommendations of the
2002 American Joint Committee on Cancer (AJCC) Cancer
Staging Manual , the prognostic relevance of which has
been validated . However, it is important to note that the
recommendations are dynamic and are intended to change
according to the state of current knowledge to optimize the
prognostic usefulness of the TNM system . Particular
attention is paid to stage groupings of the TNM system that
new data suggest contain subsets of patients with signifi-
cantly different outcome. For example, patients with
perinephric fat invasion and patients with direct ipsilateral
adrenal involvement are both pT3a, but several recent studies
suggest that adrenal involvement confers a significantly
worse prognosis [5-7]. This information may encourage a
pathologist to thoroughly sample the adrenal even in a
patient with clear evidence of perinephric fat invasion.
2. Gross description
A. How the specimen was received: fresh, in formalin,
intact, fragmented, morcellated, etc.
B. How the specimen was identified: labeled (name,
medical record number) and designated (eg, right
C. If the specimen is a radical nephrectomy, inspect the
external aspect of the specimen (Gerota fascia) for
evidence of tumor. Locate the ureteral and vascular
margins in the renal hilus. These may be sampled
before inking the specimen when they are most easily
identified. Hemostatic forceps should be placed on the
ureter so that its location remains clear during and after
inking. Ink the entire surface of the specimen.
Cannulate the ureter using a small metal probe. Open
the ureter longitudinally up to the level of the pelvis.
Place the probe into a superolateral calyx and push
through the renal parenchyma and perinephric soft
tissue. Place a second probe in an inferolateral calyx
and push through the renal parenchyma and perineph-
ric soft tissue such that the two probes are now
perpendicular to each other. Use a long, sharp knife to
bivalve the kidney starting at its convex surface along
the line of the metal probes. In this way, the kidney is
opened along the collecting system. The renal veins
should be subsequently opened in order to identify
intravenous extension of tumor. Make additional cuts
parallel or perpendicular to the first cut as necessary to
cut the neoplasm along its greatest dimensions. In
addition, cuts should be made to permit optimal
viewing of the interface between the neoplasm and the
perinephric fat because this is critical for assessing
whether the neoplasm invades the perinephric fat and
whether it approaches the margin of resection.
A partial nephrectomy may be performed for clinical
stage T1a tumors. For such specimens, ink the renal
parenchymal resection margin and breadloaf the tumor
perpendicular t o the i nked sur face. Vascular and
ureteral structures generally do not accompany partial
nephrectomy specimens. The perinephric soft tissue
will also usually not be included although sinus fat may
be and must be carefully examined if it is present (see
below). The important clinical information for partial
nephrectomies is usually only tumor type, size, and
renal parenchymal margin status, but some urologists
will submit a separate specimen consisting of overlying
perinephric fat for evaluation of tumor involvement.
D. Length of ureter, other structures included (eg, adrenal)
E. Tumor description
1. Site within the kidney: state whether the tumor is
located at the superior or inferior pole or in the mid-
portion of the kidney; if possible, determine whether
the tumor is centered on the medulla or cortex. This is
important for some tumor types (eg, collecting duct
carcinoma) in which the site of origin may support the
2. Size in 3 dimensions
3. Gross characteristics: describe the color and con-
sistency of the tissue and the degree of heterogeneity.
State whether the tissue is friable and whether there
are areas of necrosis and hemorrhage. Note and
sample any areas with a homogeneous, tan bulging
surface (so-called fish flesh quality), which may
represent sarcomatoid dedifferentiation.
4. The relationship to th e perinep hric soft tissue:
determine whether the tumor protrudes into the
perinephric soft tissue. Many renal cell carcinomas
457Renal cell carcinoma guideline
are large enough to distort the renal capsule and create
a fungiform protrusion into the perinephric soft tissue.
This alone is not sufficient to qualify as perinephric
soft tissue invasion. Determine whether the interface
between tumor and soft tissue is smooth a nd
contoured with a pushing border (features which
argue against soft tissue invasion) or irregular (a
feature which suggests soft tissue invasion). The
identification of separate tumor nodules in the
perinephric fat by gross examination is diagnostic of
pT3 disease. Under the 2002 AJCC system, extension
into the renal sinus fat is also regarded as extra renal
extension  (pT3a). In one study that specifically
addressed extension into the sinus fat, this was a vastly
more common route of perinephric soft tissue
extension . In that study, no tumor penetrated the
capsule that had not also invaded the sinus. In
addition, the earliest evidence of macroscopic venous
invasion (pT3b) is seen in the sinus fat. In fact, it has
been suggested that sinus fat involvement begins as
venous invasion, at least in clear cell carcinoma .
In comparison to patients with only perinephric fat
invasion by clear cell renal cell carcinoma, those with
sinus fat invasion appear to have a worse prognosis
. For these reasons, it is recommended that the
sinus fat be serially sectioned at 5mm intervals, and 2
sections be submitted from the interface between the
tumor and the sinus tissues .Itshouldbestated
that renal oncocytomas may extend into the perineph-
ric soft tissues, but this finding should not change the
diagnosis as they still retain their excellent prognosis.
5. Renal vein invasion: macroscopic invasion of veins
in the renal sinus and beyond indicates a pT3b
tumor. Whether the venous tumor is present only as a
thrombus or invades the venous wall should also be
noted, as the latter is associated with a worse
prognosis. Although the only assessment required by
the AJCC is whether the thrombus extends to the
diaphragm, some studies have suggested that the
prognosis is adversely affected by increasing distal
extension of the tumor thrombus [13,14]. These
studies have correlated the degree of extension with
the relationship to anatomic structures such as the
hepatic veins. Although such correlations require
clinical and/or radiological information, it is recom-
mended that a measurement be given from the tip of
the thrombus to the renal sinus.
F. Additional pathology (eg, hydronephrosis, pyelone-
phritis, arteriolonephrosclerosis): it is recommended
that an additional stain be ordered up front on the
nonneoplastic renal parenchyma. This may be either a
periodic acid–Schiff or a silver stain such as Jones
methenamine silver. These stains enhance the review
of the glomerular architecture and also serve as a
prompt to address the condition of the nonneoplastic
kidney. This is important because diseases such as
diabetic nephropathy and hypertensive nephrosclerosis
are common in the renal cell carcinoma age group .
G. Adrenal involvement: the adrenal can be reliably cleared
of involvement by renal cell carcinoma by computed
tomographic scan [16-18]. As a result, adrenalectomy
may not be performed as a component of a radical
nephrectomy. In the current TNM classification, direct
involvement of the adrenal is indicative of a pT3a tumor,
whereas if the adrenal is involved by metastatic renal
cell carcinoma, the finding requires a designation M1
and does not affect the pT classification. Several studies
have suggested that adrenal involvement even by direct
extension is an ominous finding and should warrant a
designation of pT4 [5-7].
H. Lymph nodes: involvement of regional lymph nodes is
an adverse prognostic indicator not otherwise specified
[19-21]. This appears to be true even in patients who
already have distant metastases [19,22,23]. The regional
nodes may be designated renal hilar, paracaval, aortic
(para-aortic, periaortic, lateral aortic), or retroperitoneal
. At least 80% of the time lymph nodes are not
identified in a radical nephrectomy specimen .
Based on the last 1000 radical nephrectomy specimens at
Stanford Hospital, renal hilar l ymph nodes were
identified at gross dissection in surgical pathology in
only 5% of cases. Enlarged nodes from the renal hilus are
often separately submitted by the urologist. According to
the AJCC, if a lymph node dissection is performed, it
should ordinarily include at least 8 nodes .
I. T issue submitted for special investigation: in patients less
than 20 years of age, tissue should, if possible, be
submitted for cytogenetics. Although it must be acknowl-
edged that translocation carcinomas occur across the
entire age spectrum, they represent a much higher
fraction of pediatric carcinomas . If a frozen section
of the tumor reveals an unusual morphology in an
adult patient, cytogenetics should be considered, and
frozen tissue should be procured. Although karyotypic
information may be helpful in the classification of
common types of renal cell carcinoma, its greatest value
is clearly in the diagnosis of the translocation carcinomas.
3. Diagnostic information
1. Laterality of tumor and type of resection.
2. Histologic type: the World Health Organization 2004
classification of renal cell carcinoma is recom-
a. Clear cell carcinoma
b. Multilocular cystic carcinoma
c. Papillary carcinoma
d. Chromophobe carcinoma
e. Mucinous tubular and spindle carcinoma
f. Collecting duct carcinoma
458 J. P. Higgins et al.
g. Medullary carcinoma
h. Translocation carcinomas (includes Xp11 and 6:11)
i. Tubulocystic carcinoma
j. Acquired cystic disease-associated carcinoma
k. Renal cell carcinoma, unclassified
l. Others (specify)
Outcome for renal cell carcinoma has been strongly
correlated with histologic tumor type [1,27,28],and
accurate classification of renal cell carcinomas is
essential. The different types of tumor and the
features necessary for diagnosis are very well
demonstrated in the 2004 World Health Organization
monograph . The reader is referred to that
resource for most questions of classification. Only
selected topics in classification are addressed here.
Two types of papillary renal cell carcinoma have been
recognized [30-32]. Type 1 is composed of basophilic
cells with scant cytoplasm arranged in a single layer,
whereas type 2 has more abundant, often eosinophilic
cytoplasm and pseudostratified nuclei. Some groups
have found a better prognosis for type 1 tumors
[33,34]. Although the 2 types have been demon-
strated to correlate with nuclear grade [1,35],some
authors recommend that an attempt be made to
separate papillary tumors into the 2 proposed types.
A difficulty also exists with tumors that show a
papillary architecture but clear cell cytology. Some
such tumors have been found to have cytogenetic
changes typical of clear cell carcinoma [36,37]. This
would support a practice of classifying these tumors
as clear cell carcinoma; however, the problem is in
the degree of clear cell change required in a papillary
tumor for reclassification as a clear cell carcinoma.
Salama et al  suggested 75% of the tumor cells
should be clear. This appears to be a reasonable
threshold. Focal or mild clear cell change may be
encountered in otherwise typical papillary carcino-
mas. A diagnosis of papillary carcinoma remains
appropriate for such tumors. Other tumors with
papillary architecture and clear cells may be
unclassifiable without molecular analysis; some of
these will prove to be translocation carcinomas.
3. Histological grade: it has been acknowledged that no
ideal grading scheme exists for renal cell carcinoma but
that all agree that grading of renal cell carcinoma,
however it is d one, pr ovides us eful prog nostic
information and should be performed . The Fuhr-
man scheme  is in general clinical use and has been
independently validated for clear cell and papillary
carcinomas . Most studies fail to show that grading
of chromophobe renal cell carcinomas provides
independent prediction of prognosis beyond stage.
Low-stage chromophobe carcinomas, which are often
Fuhrman grade 3, have an almost uniformly excellent
prognosis. Until novel grading systems are developed
and validated for chromophobe carcinomas, they
should not be graded . For the remaining tumors,
the overall grade should be assigned based on the
highest grade that occupies at least one 400× field  .
a. Small nuclei resembling those of mature lymphocytes
b. Larger nuclei with more open chromatin and small
c. Nucleoli readily visible on examination with 10×
d. Marked nuclear pleomorphism, multiple macronucleoli
4. Sarcomatoid dedifferentiation: a malignant spindle cell
pattern of growth has come to be recognized as a
nonspecific pattern of dedifferentiation that may occur in
any of the major types of renal cell carcinoma. The
amount of sarcomatoid tissue may be of prognostic
relevance and should be quantitated as a percentage
[34,41,42]. Either the unde rlying nonsarcomatous
carcinoma component or immunohistochemical evi-
dence of epithelial differentiation in a lesion morpholo-
gically consistent with sarcomatoid renal cell carcinoma
must be identified to permit a definitive diagnosis of
renal cell carcinoma. For cases with only a sarcomatoid
component, consideration must also be given to the
possibility of a primary or metastatic sarcoma. In
patients with sarcomatoid dedifferentiation, the already
poor prognosis is significantly further worsened by the
presence of necrosis . The amount of necrosis should
also be estimated visually in increments of 5%.
5. Presence of necrosis: coagulative tumor cell necrosis
has been found to be of prognostic significance for
both clear cell and chromophobe carcinoma
[27,34,43,44] and should therefore be reported.
6. Extent of local tumor spread: this is based on the T
component of the TNM classification.
a. Primary tumor cannot be assessed (TX).
b. There is no evidence of primary tumor (T0).
c. Tumor measures 7 cm or less and is confined to the
d. Tumor measures less than 4 cm and is confined to
the kidney (T1a).
e. Tumor measures more than 4 cm but less than 7 cm
and is confined to the kidney (T1b).
f. Tumor measures more than 7 cm but is confined to
the kidney (T2).
g. Tumor extends into major veins or directly invades
adrenal gland or perinephric fat but not beyond G
h. Tumor directly invades adrenal gland or perinephric
fat but not beyond Gerota fascia (T3a)
Assessment for perinephric fat invasion is often not straightforward.
Most renal cell carcinomas bulge into the perinephric soft tissue in a
circumscribed manner with pushing borders as noted above in the gross
description. Histologically, one should identify carcinoma cells admixed
with adipocytes without intervening fibrous tissue before diagno sing
extrarenal spread of carcinoma. We suspect that perinephric fat invasion is
often overdiagnosed in general practice and suggests that when doubt exists,
one should adhere to the requirement of carcinoma infiltrating adipocytes.
459Renal cell carcinoma guideline
i. Tumor extends into renal vein(s) segmental (muscle-
containing) branches or vena cava or its wall below
the diaphragm (T3b).
j. Tumor extends into vena cava above the diaphragm
or the wall of the vena cava (T3c).
k. Tumor extends beyond Gerota fascia (T4).
7. Microscopic evidence of angiolymp hatic invasion
should be assessed and documented.
8. Margins of resection.
a. No tumor identified at margins
b. Tumor is present at renal parenchymal margin of
resection (partial nephrectomy).
c. Tumor present at soft tissue margin of resection
d. Intravascular tumor present at venous margin of
e. Tumor is present at ureter margin
f. Others: _____________________________
9. Lymph node metastases. Not surprisingly, the presence
of lymph node metast ases a dverse ly affects the
outcome of patients with renal cell carcinoma
[22,45]. The number of nodes sampled and the number
positive should be reported. Although the prognosis
may not be adversely affected by an increasing number
of positive nodes (pN1 vs pN2)  or the size of the
largest metastatic focus, these should be reported. The
prognosis appears to be significantly adversely
affected by extranodal extension of the metastatic
focus , and therefore, it is recommended that this
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Appendix A. ASSOCIATION OF DIRECTORS OF ANATOMIC AND SURGICAL PATHOLOGY
Final Anatomic Diagnosis Checklist
RENAL CELL CARCINOMA
(Excluding Pediatric Renal Tumors and Tumors of the Renal Pelvis)
Accession No.: Part No. Date:
ORGAN: SITE: OPERATION:
Kidney Right Radical nephrectomy
Kidney and adrenal Left Radical nephrectomy and adrenalectomy
Other_________ Other_________ Other_________
_______ cm × _______ cm × _______ cm
Other gross features:
Describe appearance of tumor, location within the renal lobe with respect to cortex versus medulla if possible, presence of necrosis, extension
into the perinephric fat or the fat of the renal sinus, macroscopic invasion of veins
Tumor type (WHO 2004):
Clear cell carcinoma
-Multilocular cystic carcinoma
Papillary carcinoma (optional: specify type 1 versus type 2)
Chromophobe cell carcinoma
Mucinous tubular and spindle carcinoma
Collecting duct carcinoma
Translocation carcinomas (includes Xp11 & 6:11)
Acquired cystic disease-associated carcinoma (specify subtype)
Renal cell carcinoma, unclassified
461Renal cell carcinoma guideline
Note: These tumors, although not listed in the WHO 2004 classification, are now well-recognized and will likely be included in future editions. Any subtype
of renal cell carcinoma might be seen in the setting of acquired cystic kidney disease, but papillary and clear cell types are most common and should be reported
as such. The tumor described as “acquired cystic disease associated renal cell carcinoma” by Tickoo et al . appears to be a distinct subtype.
1 small nuclei resemble those of mature lymphocytes
2 larger nuclei with more open chromatin and small nucleoli
3 nucleoli readily visible on examination with 10x objective
4 marked nuclear pleomorphism, multiple macronucleoli
Not applicable (applies to chromophobe carcinoma)
Sarcomatoid dedifferentiation is not identified
Areas of sarcomatoid dedifferentiation are identified
Specify percentage of total tumor:____________________________________________
Depth of Tumor Invasion:
Primary tumor cannot be assessed (TX)
No evidence of primary tumor (T0)
Tumor measures 7cm or less and is confined to the kidney (T1)
Tumor measures less than 4cm and is confined to the kidney (T1a)
Tumor measures more than 4cm but less than 7cm and is confined to the kidney (T1b)
Tumor measures more than 7cm but is confined to the kidney (T2)
Tumor extends into major veins or directly invades adrenal gland or perinephric fat but not beyond Gerota fascia (T3)
Tumor directly invades adrenal gland or perinephric fat but not beyond Gerota fascia (T3a)
Tumor extends into renal vein(s) or vena cava or its segmental (muscle-containing) branches or vena cava below the diaphragm (specify
presence/absence of wall invasion) (T3b)
Tumor extends into vena cava above the diaphragm or the wall of the vena cava (T3c)
Tumor extends beyond Gerota fascia (T4)
Microscopic angiolymphatic invasion:
Margins of Resection:
No tumor identified at margins
Tumor is present at renal parenchymal margin of resection (partial nephrectomy)
Tumor present at soft tissue margin of resection
Intravascular tumor present at venous margin of resection (specific presence/absence of wall invasion)
Tumor is present at ureter margin
NOTE: retraction of vein over fully resected tumor must be excluded.
Lymph nodes (regional):
Number examined: _____________________________
Number positive: _____________________________
NOTE: Regional lymph nodes include renal hilar, paracaval, para-aortic, periaortic, lateral aortic, and retroperitonealNOS
Acquired cystic renal disease, diabetic nephropathy, arteriolonephrosclerosis, pyelonephritis, papillary adenoma, tubulopapillary
462 J. P. Higgins et al.
No histopathologic changes are present
Tumor directly invades the adrenal gland (T3a)
Adrenal involved by metastasis (M1)
Nodular/diffuse cortical hyperplasia is present
Cortical adenoma is present (specify size)
A. Primary Tumor
pTX Primary tumor cannot be assessed
pT0 No evidence of primary tumor
pT1a Tumor 4cm or less, confined to kidney
pT1b Tumor 7cm or less, confined to kidney
pT2 Tumor more than 7cm, confined to kidney
pT3a Tumor directly invades adrenal gland or perinephric tissues but not beyond Gerota fascia
pT3b Tumor grossly extends into renal vein(s) or segmental (muscle-containing) branches or vena cava or below diaphragm
pT3c Tumor grossly extends into vena cava above diaphragm or invades the wall of the vena cava
pT4a Tumor invades other organs or structures
pT4b Tumor perforates the visceral peritoneum
B. Regional Lymph Nodes
pNX Regional lymph nodes cannot be assessed
pN0 No regional lymph node metastasis
pN1 Metastasis in a single regional lymph nodes
pN2 Metastasis in more than one regional lymph nodes
C. Distant Metastasis
pMX Cannot be assessed
pM0 No distant metastasis
pM1 Distant metastasis
 AJCC Cancer Staging Manual. Lippincott-Raven Press, 6
edition, 2002 (pg. 323-325).
 Tickoo SK, dePeralta-Venturina MN, Harik LR, et al. Am J Surg Pathol. 2006;30:141-53.
463Renal cell carcinoma guideline