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Recommendations for the Reporting of Surgically Resected Specimens of Renal Cell Carcinoma

DOI: http://dx.doi.org/10.1309/AJCP84ESGXKXYNRA 623-630 First published online: 1 May 2009
Key Words:
  • Surgical pathology
  • Staging
  • Histology
  • Histopathology

Scope of the Guidelines

The reporting of renal cell carcinoma is facilitated by the provision of a checklist to ensure 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 morphologic types of renal 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 are driven by the behavior of clear cell carcinoma, the overwhelmingly most common subtype.

Several aspects of renal cell carcinoma classification remain problematic. Despite 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 carcinoma have been proposed but do not clearly have prognostic relevance independent of nuclear grade.1 The grading scheme proposed by Fuhrman et al2 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 applicable 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 attempts to address these problematic points and suggest reasonable means of providing the information called for in the accompanying checklist.

Features the Association Recommends for Inclusion in the Final Report

These features are selected on the basis that they are generally accepted as being of prognostic importance, required for therapy, and/or traditionally expected. The guidelines adhere to the recommendations of the 2002 American Joint Committee on Cancer (AJCC) Cancer Staging Manual,3 the prognostic relevance of which has been validated.4 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.3 Particular attention is given to stage groupings of the TNM system that new data suggest contain subsets of disease with significantly different outcome. For example, patients with perinephric fat invasion and patients with direct ipsilateral adrenal involvement have pT3a disease, but several recent studies suggest that adrenal involvement confers a significantly worse prognosis.57 This information may encourage a pathologist to thoroughly sample the adrenal even in a patient with clear evidence of perinephric fat invasion.

I. Gross description

  1. How the specimen was received: eg, fresh, in formalin, intact, fragmented, morcellated

  2. How the specimen was identified: labeled (name, medical record number) and designated (eg, right radical nephrectomy).

  3. If the specimen is a radical nephrectomy specimen, 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. A 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 perinephric soft tissue such that the 2 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 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 “bread loaf” the tumor perpendicular to the inked surface. 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 E, “Tumor description,” No. 4). 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.

  4. Length of ureter, other structures included (eg, adrenal)

  5. 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 information is important for some tumor types (eg, collecting duct carcinoma) in which the site of origin may support the diagnosis.

    2. Size in 3 dimensions

    3. Gross characteristics: Describe the color and consistency 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 the perinephric soft tissue. Determine whether the tumor protrudes into the perinephric soft tissue. Many renal cell carcinomas are large enough to distort the renal capsule and create a fungiform protrusion into the perinephric soft tissue, which alone is not sufficient to qualify as perinephric soft tissue invasion. Determine whether the interface between tumor and soft tissue is smooth and contoured with a pushing border (features that argue against soft tissue invasion) or irregular (a feature that 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 extrarenal extension8 (pT3a). In 1 study that specifically addressed extension into the sinus fat, this was a vastly more common route of perinephric soft tissue extension.9 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.10 In comparison with patients with only perinephric fat invasion by clear cell renal cell carcinoma, patients with sinus fat invasion seem to have a worse prognosis.11 For these reasons, it is recommended that the sinus fat be serially sectioned at 5-mm intervals and 2 sections be submitted from the interface between the tumor and the sinus tissues.12 It should be stated that renal oncocytomas may extend into the perinephric soft tissues, but this finding should not change the diagnosis because they still have an 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 because the latter is associated with a worse prognosis. While 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 radiologic information, it is recommended that a measurement be given from the tip of the thrombus to the renal sinus.

  6. Additional pathology (eg, hydronephrosis, pyelonephritis, arteriolonephrosclerosis): It is recommended that an additional stain be ordered up-front on the nonneoplastic renal parenchyma. This stain may be 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.15

  7. Adrenal involvement: Involvement of the adrenal by renal cell carcinoma can be reliably determined by computed tomography scan.1618 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 of 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 pT4.57

  8. Lymph nodes: Involvement of regional lymph nodes is an adverse prognostic indicator.1921 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, or lateral aortic), or retroperitoneal, not otherwise specified.3 At least 80% of the time, lymph nodes are not identified in a radical nephrectomy specimen.24 Based on the last 1,000 radical nephrectomy specimens at Stanford Hospital, Stanford, CA, renal hilar lymph 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.3

  9. Tissue submitted for special investigation. In patients younger than 20 years, tissue should, if possible, be submitted for cytogenetics. Although it must be acknowledged that translocation carcinomas occur across the entire age spectrum, they represent a much higher fraction of pediatric carcinomas.25 If a frozen section of the tumor reveals unusual morphologic features in an adult, 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 translocation carcinomas.

II. Diagnostic information

  1. Laterality of tumor and type of resection

  2. Histologic type: the World Health Organization 2004 classification of renal cell carcinoma is recommended.26

    1. Clear cell carcinoma

    2. Multilocular cystic carcinoma

    3. Papillary carcinoma

    4. Chromophobe carcinoma

    5. Mucinous tubular and spindle carcinoma

    6. Collecting duct carcinoma

    7. Medullary carcinoma

    8. Translocation carcinomas (include Xp11 and 6:11)

    9. Tubulocystic carcinoma

    10. Acquired cystic disease–associated carcinoma

    11. Renal cell carcinoma, unclassified

    12. Other (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.29 Readers are referred to that resource for most questions of classification. Only selected topics in classification are addressed herein.

    Two types of papillary renal cell carcinoma have been recognized.3032 Type 1 carcinomas are composed of basophilic cells with scant cytoplasm arranged in a single layer, whereas type 2 carcinomas have 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 demonstrated 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 papillary architecture but clear cell cytologic features. 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 and coworkers37 suggested 75% of the tumor cells should be clear. This seems to be a reasonable threshold. Focal or mild clear cell change may be encountered in otherwise typical papillary carcinomas. 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. Histologic 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 done, provides useful prognostic information and should be performed.38 The Fuhrman scheme2 is in general clinical use and has been independently validated for clear cell and papillary carcinomas.39 The majority of 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.40 For the remaining tumors, the overall grade should be assigned based on the highest grade that occupies at least 1 x400 field39:

    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

  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 underlying nonsarcomatous carcinoma component or immunohistochemical evidence of epithelial differentiation in a lesion morphologically 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.41 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 clear cell and chromophobe carcinomas27,34,43,44 and should therefore be reported.

  6. Extent of local tumor spread: This extent is based on the T component of the TNM classification.

    1. Primary tumor cannot be assessed (TX)

    2. No evidence of primary tumor (T0)

    3. Tumor measures 7 cm or less and is confined to the kidney (T1)

    4. Tumor measures less than 4 cm and is confined to the kidney (T1a)

    5. Tumor measures more than 4 cm but less than 7 cm and is confined to the kidney (T1b)

    6. Tumor measures more than 7 cm but is confined to the kidney (T2)

    7. Tumor extends into major veins or directly invades adrenal gland or perinephric fat but not beyond Gerota fascia (T3)

    8. Tumor directly invades adrenal gland or perinephric fat but is not beyond Gerota fascia (T3a)*

    9. Tumor extends into renal vein(s) segmental (muscle containing) branches or vena cava or its wall below the diaphragm (T3b)

    10. Tumor extends into vena cava above the diaphragm of the wall of the vena cava (T3c)

    11. Tumor extends beyond Gerota fascia (T4)

      *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 in the gross description section. Histologically, one should identify carcinoma cells admixed with adipocytes without intervening fibrous tissue before diagnosing extrarenal spread of carcinoma. We suspect that perinephric fat invasion is often overdiagnosed in general practice and suggest that when doubt exists, one should adhere to the requirement of carcinoma infiltrating adipocytes.

  7. Microscopic evidence of angiolymphatic invasion should be assessed and documented.

  8. Margins of resection

    1. No tumor identified at margins

    2. Tumor present at renal parenchymal margin of resection (partial nephrectomy)

    3. Tumor present at soft tissue margin of resection

    4. Intravascular tumor present at venous margin of resection

    5. Tumor is present at ureter margin

    6. Other

  9. Lymph node metastases: Not surprisingly, the presence of lymph node metastases adversely 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)22 or the size of the largest metastatic focus, these should be reported. The prognosis seems to be significantly adversely affected by extranodal extension of the metastatic focus,24 and, therefore, it is recommended that this be assessed and reported as well.


Accession No.:Part No.Date:
Patient Name:
KidneyRightRadical nephrectomy
Kidney and adrenalLeftRadical nephrectomy and adrenalectomy
Partial nephrectomy
Specimen Weight (Required) ______________________________
Tumor Size (Required) _________x________x________cm
Other Gross Features (Required)
  Describe appearance of tumor, location within the renal lobe with respect to cortex vs medulla, if possible, presence of necrosis, extension into the perinephric fat or the fat of the renal sinus, macroscopic invasion of veins
Tumor Type (World Health Organization 2004) (Required)
  • Clear cell carcinoma

    Multilocular cystic carcinoma

  • Papillary carcinoma (optional: specify type 1 vs type 2)

  • Chromophobe cell carcinoma

  • Mucinous tubular and spindle carcinoma

  • Collecting duct carcinoma

  • Medullary carcinoma

  • Translocation carcinomas (includes Xp11 and 6:11)*

  • Tubulocystic carcinoma*

  • Acquired cystic disease associated carcinoma (specify subtype)*

  • Renal cell carcinoma, unclassified

  • Other________________________________________________________

* These tumors, although not listed in the 2004 World Health Organization 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 al1 appears to be a distinct subtype.
Histologic Grade (Required)
      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 x10 objective)
      4 (marked nuclear pleomorphism, multiple macronucleoli)
  Not applicable (applies to chromophobe carcinoma)
Sarcomatoid Dedifferentiation
  Sarcomatoid dedifferentiation is not identified
  Areas of sarcomatoid dedifferentiation are identified
  Specify percentage of total tumor:___________________________
Depth of Tumor Invasion (Required)
  Primary tumor cannot be assessed (TX)
  No evidence of primary tumor (T0)
  Tumor measures 7 cm or less and is confined to the kidney (T1)
  Tumor measures less than 4 cm and is confined to the kidney (T1a)
  Tumor measures more than 4 cm but less than 7 cm and is confined to the kidney (T1b)
  Tumor measures more than 7 cm 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 (Required)
  Not identified
Margins of Resection (Required)
  No tumor identified at margins
  Tumor 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 or absence of wall invasion)*
  Tumor is present at ureter margin
* Retraction of vein over fully resected tumor must be excluded.
Lymph Nodes, Regional* (Required)
  Number examined_________________________________
  Number positive__________________________________
* Regional lymph nodes include renal hilar, paracaval, para-aortic, periaortic, lateral aortic, and retroperitoneal, not otherwise specified.
Additional Findings (Required)
  Acquired cystic renal disease, diabetic nephropathy, arteriolonephrosclerosis, pyelonephritis, papillary adenoma, tubulopapillary hyperplasia, cysts
Adrenal Gland (Optional)
  No histopathologic changes present
  Tumor directly invades the adrenal gland (T3a)
  Adrenal involved by metastasis (M1)
  Nodular/diffuse cortical hyperplasia present
  Cortical adenoma is present (specify size)
Ancillary Studies (Optional)
pTN Stage2 (Required)
  A. Primary tumor
    pTX Primary tumor cannot be assessed
    pT0 No evidence of primary tumor
    pT1a Tumor 4 cm or less, confined to kidney
    pT1b Tumor 7 cm or less, confined to kidney
    pT2 Tumor more than 7 cm, 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 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 node
    pN2 Metastasis in more than 1 regional lymph node
  C. Distant metastasis
    pMX Cannot be assessed
    pM0 No distant metastasis
    pM1 Distant metastasis
  • References

  • 1. Tickoo SK, dePeralta-Venturina MN, Harik LR, et al. Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia. Am J Surg Pathol. 2006;30:141–153.

  • 2. Greene FL, Page DL, Fleming ID, et al; for the American Joint Committee on Cancer, eds. Cancer Staging Manual. 6th ed. New York, NY: Springer; 2002:323–325.

  • 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)


    • * Committee members are John P. Higgins, MD (chair),1 Jesse K. McKenney, MD,1 James D. Brooks, MD,2 Pedram Argani, MD,3 and Jonathan I. Epstein, MD,3 from the Departments of 1Pathology and 2Urology, Stanford University, Stanford, CA; and 3Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.


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