various aspects of renal cell carcinoma staging

1. Renal cell carcinoma staging: pitfalls, challenges and
updates
Sean R Williamson,Kanika Taneja & Liang Cheng;
Department of Pathology and Laboratory Medicine and Henry Ford
Cancer Institute, Department of Pathology and Laboratory Medicine,
Wayne State University School of Medicine, Detroit, MI

2. -Renal cell carcinoma (RCC) is unusual among cancers -grows
as a spherical, well-circumscribed mass.
-Increasing tumour size influences the pathological pT stage
category within pT1 and pT2(cutoffs of 40, 70 and 100 mm)
size - in thelikelihood of renal sinus or renal vein
tributary invasion
INTRODUCTION

3. RCC Vs Classical carcinoma
Features RCC Classic ca
Infiltrative growth,
desmoplastic
reaction, mitotic
activity, and
necrosis.
Often lacks many of
these features Present
Gross
Rounded or spherical
and well circumscribed Absent
Cytological atypia Limited Present

5. pT1/pT2 subclassification
pT1a - tumour size of ≤40 mm
pT1b - tumour size of >40–70 mm
pT2a – tumour size of >70–100 mm
pT2b – tumour size of >100 mm
No
extrarenal
or
venous
extension

7. SIZE DETERMINATION
When the largest dimension of the tumour is
perpendicular to the plane of section of the mass
some reconstruction is required after determination of
the extent of the tumour.
Tumour size can vary between that measured by
imaging and that measured in unfixed and fixed
pathological specimens.

8. Imaging modalities can slightly overestimate the
tumour size as compared with the pathological specimen
(minimal difference of 1–3 mm).
Size discrepancy may be greatest for smaller tumours.
There is also some evidence that tumour size decreases
slightly after formalin fixation.

9. Size assessment of predominantly cystic
tumours
 Multicystic tumour with neoplastic cells throughout
should be measured in the GD irrespective of the cystic
component.
 Solid nodule in the wall of a single cyst  raises the
question ????????

10. Remember the likelihood of extrarenal extension(renal sinus
invasion)
Renal sinus invasion increases dramatically with tumour
size.
Bonsib et al, found that only 32% of clear cell
RCCs of >40 mm were limited to the kidney, and this
decreased to 3% for tumours of >70 mm.

11. Renal sinus invasion was first added to the AJCC TNM
staging system as pT3a in the 2002 revision.
Bonsib et al., have shown that invasion of the renal sinus is
a key invasive pathway, especially for clear cell
RCC.
pT3 subclassification
RENAL SINUS INVASION:

13. Sample the entire renal sinus and tumour interface for
large clear cell tumours(>40 or >50 mm)
Sample two or three tissue blocks of the tumour–renal
sinus interface for tumours with a lower suspicion for renal
sinus invasion.
SAMPLING CLEAR CELL RCC

14. ARBITRARY POINT
Involvement of veins in the renal sinus (in the absence of
direct soft tissue involvement) should be considered to be
vein or vein branch invasion, renal sinus invasion, or both.
Report large vein or vein branch invasion as such, and to use
the term renal sinus invasion for direct soft tissue or smaller
lymphovascular invasion in the renal sinus.

15. RCC has a peculiar tendency to invade as large, finger-like
structures into vein branches.
Can be removed with a nephrectomy specimen, particularly
when they do not invade or adhere to the vein wall.
RENAL VEIN AND VEIN BRANCH INVASION

17. Smaller venous nodules show a rounded contour,that they can be
underappreciated and regarded as tumour multinodularity.

20. Involvement of the main renal vein (visible at the
hilum) is more significant than segmental vein branch
invasion.
Confers a significant recurrence risk.

21. AJCC 2016 TNM classification:
vein invasion be recognised grossly
vein walls contain muscle for the diagnosis of vein
invasion.
WHAT’S NEW?

23. Renal vein margin evaluation
ISUP recommendation
Positive when tumour is histologically adherent to or
invading the vein wall at the margin
Negative the tumour extension is freely mobile within the
vein at the margin and confirmed histologically,

24. How to sample?????
Amputate the distal-most vein wall crosssection,
including the tumour.
Trim the vein wall separately from the tumour with
scissors (if the wall is freely mobile)

27. RETROGRADE VENOUS INVASION
Occlusion of the main renal vein by tumour
Backwards spread within vein branches
Result in multiple ‘satellite’ tumour nodules
Found in approximately 5–8% of RCCs.

29. VENA CAVA INVOLVEMENT
pT3b - extension to the vena cava below the
diaphragm
pT3c - including extension above the diaphragm
or invasion of the vena cava wall
pT3 stage

30. HOW TO ASSESS????
Any additional specimen of ‘tumour thrombus’ be sampled
histologically.
Assess for incorporation of vein wall into the tumour or
adherence of intimal or medial-type tissue to the tumour.

31. PERINEPHRIC FAT INVASION(pT3a)
Usually occurs in addition to renal sinus or vein invasion.
It is critical to select histological sections to offer a full
view of the relationship of the tumour border with the
renal capsule or tumour pseudocapsule and perinephric
fat

34. RENAL PELVIS INVASION
pT3a in the current scheme
 A finger-like or polypoid nodule of tumour within the
collecting system would be considered to be pT3a

35. Lymphovascular invasion
Not a direct staging parameter in the AJCC TNM
system.
Microscopic lymphovascular invasion as a small tumour
plug within a lymphovascular space
Distinct nodule on macroscopic inspection of the
slide  tributary vein invasion

37. pT4 subclassification
Includes:
direct invasion of the ipsilateral adrenal gland
invasion of the Gerota fascia.
Non-contiguous nodule in the adrenal gland is
regarded as pM1.

38. Incidental benign adrenal cortical nodules and
adenomas and have
Similar gross appearance to RCC (golden yellow)
Similar microscopic appearance (cells with clear
cytoplasm,arranged in nests).
THE CHALLENGE!!
Adrenal cortical tissue and nodules usually have
extensively vacuolated morphology.

39. Gerota fascia involvement  Used when tumour extends
to the soft tissue surface of the specimen
Use ink only when there is suspicion for extension to
some surface of the specimen
Direct invasion of the liver also fit in the pT4
category.

40. Lymph nodes
In current practice, lymph nodes are not routinely
dissected by urologists in all RCC cases
The ISUP handling guidelines:
Palpation and dissection of the hilar area to be
performed (as this is the area most likely to contain
lymph nodes)

41. LND can be considered in selected cases
 larger tumors
 locally advanced diseases
 unfavorable pathological characteristics
due to the risk of associated nodal metastases and
possible benefit in terms of cancer control.

42. Non-hilar lymph nodes were also found, with
a lower rate of positivity (65% hilar; 16% nonhilar)
Some attention should be paid to possible lymph nodes
in other areas of nephrectomy specimens.
Extranodal extension of tumour may be more
important than the number of lymph nodes involved.

43. Distant metastases
Surprising sites  such as Gallbladder.
An interesting site that appears to be enriched for RCC
metastases is the Pancreas (may benefit from surgical
resection).

44. RCC may mimic primary tumours of the pancreas.
The Diagnostic challenge
Pancreatic endocrine tumours
Serous cystadenomas
Solid pseudopapillary neoplasms

45. Pancreatic endocrine tumours and serous cystadenomas
are von Hippel–Lindau disease-associated tumours.
PAX8 is probably a helpful immunohistochemical
marker in the distinction of RCC from neuroendocrine
tumours

46. In metastases to lung,bone and lymph nodes
Consider patient’s renal mass or renal cancer history
Render the diagnosis of metastatic RCC.

47. Large renal mass or a k/h/o resection of a high-stage renal mass
Metastatic tumour with appropriate RCC morphology
Positive IHC staining results
Certainity of diagnosing RCC is typically high.

48. Organ-confined RCC of large size (>40–50 mm)
may have had vascular or renal sinus invasion that
was originally not detected.
Metastatic RCC of uncertainity
Small renal mass or the lack of an appreciable renal
mass

49. RCC includes a heterogeneous group of tumours with
some unusual clinical and pathological characteristics that
contrast with those of other cancers.
SUMMARY
With increasing interest in adjuvant therapy in renal cancer,
the pathologist’s role in RCC staging will continue to be an
important prognostic parameter and a tool for selection of
patients for enrolment in clinical trials.

50. Larger tumours
Tumours with any
deviation from a
spherical shape
(especially finger-like
protrusions)
extreme suspicion for
vascular or renal
sinus invasion

51. Thoroughly sample the renal sinus interface.
Representative sampling of the tumour to perinephric fat
(two sections or more with adherent fat or mushroom-shaped
outpouching into the fat)is necessary.

52. THANK YOU

53. Histopathological Prognostic Factors in Clear Cell
Renal Cell Carcinoma
.
Vol. 44, No. 3, 2018 July-September
BIANCA CĂTĂLINAANDREIANA,ALEX EMILIAN STEPAN.,et al,
Department of Morphopathology,University of Medicine and Pharmacy of
Craiova

54. To determine the incidence and relation between prognosis
factors in Clear cell RCC
- Pattern
- Fuhrman grade
- Tumor stage
- Vascular invasion
- Necrosis
- Sarcomatoid transformation
AIM

55. Introduction
Clear cell renal cell carcinoma (CCRCC) - the most
common (70%) histological subtype of RCC.
Male:Female-2:1
6-7 decade of life

56. Tumor stage
Fuhrman
grade
Tumor
necrosis
Sarcomatoid
transformation
Fat and
vascular
invasion
Progression and metastasis
of CCRCC

57. Most used scale in CCRCC classification.
- Low grade CCRCC (Fuhrman 1 and 2)  better prognosis
- High grade CCRCC (Fuhrman 3 and 4) bad prognosis
Fuhrman nuclear grade

58. Tumor stage
Important prognosis factor in CCRCC
Correlates with
-Tumor size
-Vascular invasion
-Tumor necrosis
-5-year survival rate
Sarcomatoid transformation or tumor
necrosis,even in focal form, was associated
with bad prognosis

59. This study was performed on 75 cases of CCRCC
diagnosed in the Anatomical Pathology Laboratory of the
County Clinical Emergency Hospital of Craiova between 2014
and 2017.
The biological material was represented by pieces of
nephrectomy.
The cases were analyzed on two criteria: epidemiology and
histopathology.
Statistical analysis - Chi Square tests.
MATERIALS AND METHODS

60. RESULTS

62. Fuhrman grade 1 CCRCC
CCRCC with fat invasion

63. CCRCC with vascular invasion
CCRCC with sarcomatoid
transformation

64. CCRCC with mixed pattern

65. Clear cell renal cell carcinoma are the mostfrequent malignant
renal neoplasms.
Originate in the renal tube epithelia and most of them show an
invasive growth pattern.
Most CCRCC were identified in male patients(66.6%).
The average diagnosis age was 59.8±10.2 years, extreme ages
being 33 and 80 years
DISCUSSION

66. Fuhrman grade and tumor stage are considered to be the most
important prognostic factors in CCRCC.
Multiple studies indicate Fuhrman grade as a prognostic factor
for survival, independent from pathologic stage.
High Fuhrman grade CCRCC were significantly associated
with advanced tumor stage (p<0.05, χ2 test)
Most cases presented a mixed pattern, significantly associated
with advanced tumor stages (p<0.05, χ2 test).

67. No significant association between Fuhrman grade, vascular
invasion and tumor necrosis.
Significant correlation was found between tumor stage and
vascular invasion.
Even though the presence of sarcomatoid transformation
was more frequent in advanced tumor stages, it wasn’t
significantly linked to them (p>0.05, χ2 test).

68. Histopathological parameters are important prognostic factors in
CCRCC.They prove useful in determining the aggressiveness of
the carcinoma.
CCRCC in advanced tumor stages is associated with high
Fuhrman grade and mixed architectural pattern.
CONCLUSION

69. THANK YOU