Small Renal Mass: Is there a place for Renal Biopsy ?

1. Small Renal Mass: Is there a
place for Renal Biopsy ?
Dr. Elsayed SALIH M.D.
Associate professor of urology
Al-Azhar university

2. In the management of SRMs
 What is the natural history of small renal
masses (SRMs) ?
 What are the safety, technical
considerations, outcomes and roles of RMB
?

3. Introduction
 2-3% of all newly diagnosed cancers are RCCs.
 Incidental detection of SRMs increased
 More broad use of abdominal imaging
 Except for large typical angiomyolipoma, imaging alone
cannot accurately characterize

4. Introduction
 SRM : all renal masses with a diameter ≤ 4 cm;
 SRM: 40‒70% of incidentally discovered renal tumours
 SRM: management is challenging
 RMB used for tissue sampling better characterization
 In the past, RMB limited due to:
i. safety,
ii. Accuracy
iii. impact on clinical decision-making.
(Leão et al, 2016)

5. Why characterization of SRM by RMB become
a step forward in our management??
 THREE REASONS
1. 20‒30% of SRM are benign not need active treatment.
2. Detection the origin of renal tumour a primary or a
secondary malignancy.
3. Detection of the histological subtype and aggressiveness.

6. Management of SRM
 Partial nephrectomy is the gold standard
 alternatives in patients not fit or refuse surgery.
1. Active surveillance
2. ablation therapy, such as cryotherapy and radiofrequency,

7. Even Nephron Sparing approaches have
potential side effects

8. How Do We Balance Tumor, Patient
Factors, and Risks to Help Patients Make
Informed Decisions About Management
of SRMs?

9. Natural history of small renal masses
 Most SRMs are RCCs,
 Treatment results are excellent
 >90% disease-specific survival at 5 year.
 Not all SRMs are malignant 20-30% will be benign (e.g.:
1. Angiomyolipoma,
2. Oncocytoma,
3. Metanephric adenoma

10. Natural history of small renal masses
 Not all have similar growth potential.
 there is concern about the morbidities of treatment for
potentially indolent lesions.
 the incidence of kidney cancer is increasing BUT
mortality has not increased proportionately.

11. Natural history of small renal masses
 many SRMs have a low malignant potential not need
aggressive initial treatment.
 Understanding the biologic behaviour and natural history of
SRMs will improve the prediction of
1. Local tumour growth
2. Stage progression
3. Metastatic potential

12. Natural history of small renal masses
 In one series (n ¼ 151), only 2 patients (1%) reported to
have progressed to metastatic disease.
 The observed overall growth rate was relatively slow (0.13
cm/yr),
 with two thirds of SRMs (100/151, median follow-up of
29mo) showing slow or no growth at all.
(Jewett et al, 2011)

13. Natural history of small renal masses
 In other studies: lesions between 3 cm and 4 cm have
aggressive pathological features .
 These results highlight the heterogeneous behavior of SRMs.
 Factors predict malignancy: initial tumour size, age and
growth rate.
 these variables, not validated for clinical utility in the
prediction of biologic behaviour of renal lesions.

14. Natural history of small renal masses
 to characterize SRMs in the absence of validated imaging
or other biomarkers RMB.
 RMB provides information about
1. Benign vs malignant tumours
2. Heterogeneous behaviour before a treatment decision

15. Current indications of renal tumour biopsies
 Pretreatment RMB continues to be debated.
 RMBs was traditionally reserved to
1. diagnose secondary malignancy,
2. metastatic renal tumours
3. benign non-tumour pathology as renal abscess.

16. Current indications of renal tumour biopsies
 More recently,
1. diagnosis recurrence post-ablative therapy
2. characterize the RCC subtype in metastatic disease to select
biological systemic therapy
 RMBs should be offered to most, if not all patients with a SRM
to help guide clinical management.

17. Contraindications for RMB
 The absolute: uncorrectable coagulopathy.
 Relative: patients with short life expectancy who are not
candidates for any treatment

18. Technique of RMB
 Image-guidance
 Methods: Fine needle aspiration (FNA)
versus needle core biopsies
 Needle size
 Number of cores in core biopsies

19. Image-guidance
 RMBs outpatient. local anesthetic
 using either ultrasound or CT guidance.
 US guidance favored:
1) advantages of real-time visualization of the tumour,
2) lower cost
3) avoidance of ionizing radiation
 Body habitus and tumour location are considerations.
 CT is more useful for deeply located lesions

20. FNA versus needle core biopsies
 FNA: tumour cells are aspirated during multiple needle passes
 needle core biopsy is taken with a double action needle, usually
through a coaxial sheath.
 Both sample one area of the tumour mass per pass
 Redirection of the needle for sampling other areas.
 Needle cores are preferred form of biopsy.
 FNAs:
1) Lower diagnostic rates
2) Lower histologic architectural examination.

21. Needle size and number of cores in core
biopsies
 larger bore needles (14- and 18-gauge) most accurate for
histological diagnosis
 Most centers use 18-gauge
 The optimal number of cores not defined.
 increasing the number of cores, improve the diagnostic rate.
 at least two cores should be taken

22. Single or multiquadrant biopsy
 Single biopsy:
1. Not representative of the landscape of genomic tumour abnormalities
2. May miss the heterogeneous area in mixed tumour.
 Multiquadrant biopsy:
1. Decrease previous risk
2. important in era molecular and genetic studies.

23. Tumour characteristics associated with
a diagnostic biopsy
 Diagnosis correlate with
1. Increasing tumour size, including the size of solid components
of cystic tumours,
2. Location of tumour
 the larger SRMs and an exophytic location more diagnostic.
 RMB of cystic lesions were less diagnostic

24.  RMB usually non-diagnostic in tumours <1 cm in diameter so
initial active surveillance is considered.
 RMBs considered for growing lesions once tumours reach >1 cm
 False negative biopsy in:
1. Needle misses,
2. Tumour necrosis
3. Tumour heterogeneity
Tumour characteristics associated with
a diagnostic biopsy

25.  Safe and well tolerated.
 Major complications rare (<1%).
 90% of complication is Minor bleeding
 Haemorrhage necessitating blood transfusion is rare
 The risk of bleeding greater with larger bore (<18-gauge) needles.
 Other potential complications:
1. Infection,
2. Pneumothorax (<1%)
3. Arteriovenous fistula
Safety of RMB

26. Tumour seeding
 few cases of tumour seeding along the needle track reported and
the majority were before 2001.
 Explanation:
the coaxial sheath decreased the direct contact of the needle
with the surrounding tissue so decrease risk of seeding.

27. Diagnostic performance
 A number of large series have recently assessed the diagnostic
performance of renal biopsy in SRM (Burruni et al. 2016)

28. Diagnostic performance
 Each series included a median of 105 patients (IQR 83‒150)
 Median tumour volume of 33 mm (IQR 27‒40).
 89% of patients had solid lesions, 11% presenting cystic lesions.
 The median rate of diagnostic renal biopsies 86%,
 Diagnosis of malignancy in a median of 79%.

29. Nondiagnostic biopsy
 Due to insufficient material or the presence of normal parenchyma.
 Nondiagnostic biopsy is usually the result of inaccurate sampling.
 Repeat biopsy lead to a histological diagnosis in 83.3% patients in
which initial biopsy was nondiagnostic.
 most nondiagnostic biopsies with cystic lesions, with a median of
29% nondiagnostic rate in this subgroup 14% nondiagnostic
biopsies in solid lesions.

30. Diagnostic accuracy
 Sum of true positives and true negatives divided by the total number
of patients
 Determined by nephrectomy specimen as the reference test.
 Outcomes affect biopsy accuracy include:
1. Presence of malignancy,
2. Histological subtype,
3. Fuhrman grade.
 To distinguishing malignant and benign lesions, the median accuracy of
RMB excellent at 98%
 To determining histological subtype with a median of 92%.

31. Diagnostic accuracy
 Improved by using immunohistochemical and molecular
techniques.
 In determining Fuhrman grade was lower, with a median of 72%.
 The grade heterogeneity is a common feature in renal carcinoma
and might be the reason for the discrepancy between biopsy and
final pathology.
 upgrade in Fuhrman grade from biopsy samples to final pathology
can be expected.

32. Example of interest of immunohistochemistry in renal biopsy in order to distinguish oncocytoma (a-b)
from cromophobe carcinoma (c-d). This distinction is of key importance to guide further management.
Although both are eosinophilic tumours, oncocytoma cells usually show indistinct margins and cell
nuclei may have nonhomogeneous shape and present large fibroedematous stroma (a). Cromophobe
carcinoma cells usually present distinct margins, cells are smaller and nuclei are rounded (c). Both
tumours express CK7, but the pattern is different. While oncocytoma show focal or limited expression in
most cases (b), cromophobe carcinoma show intensive and extended CK7 expression (d).
(Burruni et al. 2016)

33. Role of RMB in clinical decision
 treatment modality is based on patient age, clinical assessment of
patient comorbidities, renal function and tumour characteristics.
 Non-adopters of routine RMBs RMB will not affect the clinical
management.
 RMBs SRM surgical and ablation rate if benign disease is initially
observed.
 Despite improvements in imaging, benign lesions cannot be
accurately identified.

34. Role of RMB in clinical decision
 In Toronto cohort, 41% avoided definitive treatment following
biopsy either because
1. have a benign tumour,
2. favourable histology
3. presence of metastatic disease of another primary origin
 Maturen et al. have shown that the biopsies significantly impacted
on clinical management in 61% of their cohort, which was defined
as a change in proposed management from surgery and no surgery

35. US guided biopsy in a 60-year-old woman with known anal carcinoma.
(a) Staging abdominal CT scan shows a 2 cm hypodense mass (red arrow) on the right lateral part of a
horseshoe kidney;
(b) Coronal reconstructions depicting the nodule on the same CT scan;
(c) US guided biopsy performed with an 18 G needle (green arrow) revealed an epithelioid
angiomyolipoma. (Burruni et al. 2016)

36. Role of RMB in clinical decision
 Selecting active surveillance candidates.
 Active surveillance depend on the natural history of SRMs.
 The active surveillance protocols are built on tumour kinetics
 Non-growing or slow growing tumours have a low likelihood of
metastatic progression so suitable for initial follow-up
 Growth rate alone is not sufficient to differentiate between benign
and malignant lesion.

37. Role of RMB in clinical decision
 Thermal ablation as RFA and cryoablation used for SRMs in the
elderly and infirm.
 Pre-ablation RMB
1. Not universally accepted,
2. Define treatment success
3. Interpret the need for additional treatment if needed
4. Defines follow-up.
5. Performed before the treatment decision to reduce the risk
of unnecessary treatment

38. US guided biopsy in an obese 42-year-old woman (BMI 33).
(a) Incidentally identified small solid nodule of the left kidney (red arrow) on abdominal CT scan;
(b) Percutaneous US-guided 18 G needle biopsy (green arrow) revealed a chromophobe carcinoma;
(c) Percutaneous radiofrequency was performed and three-months MRI (blue-blue coloured)
compared to preoperative CT scan (orange-coloured) showed complete ablation.
(Burruni et al. 2016)

39. The future of RMBs in SRM management
 Future goals:
1. Improving ability to obtain samples
2. Reliable and accurate sampling of the tumour
3. New tissue markers
4. The role of heterogeneity in SRMs, mainly in
treatment and follow-up.

40. The future of RMBs in SRM management
 RMBs detect biological aggressiveness which is of great potential
clinical value.
 For example,
a high grade lesion (extensive sarcomatoid or rhabdoid features)
may be managed more appropriately by more aggressive therapy
(e.g., radical nephrectomy rather than partial nephrectomy,
thermalablation therapy or active surveillance.

41. The future of RMBs in SRM management
 Carbonic anhydrase IX (CAIX) has prognostic implications.
 Diagnostic and prognostic information can be obtained with
1. Immunohistochemistry (IHC),
2. Cytogenetic and molecular analysis
3. Gene expression profiling

42. The future of RMBs in SRM management:
improving the accuracy of IHC
 An IHC antibody panel, including
1. CD10,
2. parvalbumin, a-methylacyl-coenzyme A racemase (AMACR),
3. cytokeratin 7 (CK7),
4. S100A1,
5. cathepsin K
6. CAIX, seems to be the most promising.
 RNA based assays;
 Fluorescence in situ hybridization (FISH) studies: analyzing
chromosomal abnormalities

43.  The consensus meeting was held on 6 June 2012, at the start of the 5th International Symposium
on Focal Therapy and Imaging in Prostate and Kidney Cancer (Durham, NC, USA,
http://www.focaltherapy.org).
 The panel was tasked with focusing on the role of biopsy in the management of SRMs.
 BJU Int 2014; 113: 854–863

44. Detailed topics and specific items set
discussed by the panel.

45. Recommendations for technical standards of RMB.

46. statements on topic regarding pathological
interpretation of biopsy samples.

47. Statements on indications for RMB.

48. Highlights
 SRMs are enhancing kidney tumours 4 cm that are usually incidentally detected. Most,
but not all, are RCCs.
 SRMs are usually treated as RCC. As a result, benign tumours and low grade RCCs of
uncertain biology are being treated in over 20% of cases.
 Pretreatment RMB can reduce potentially unnecessary treatment
 RMB is safe, only a 1% incidence of significant complications
 RMB, together with molecular and genetic studies will improve our knowledge of SRMs
 RMB has a high diagnostic yield and accuracy, and is cost effective.