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74 Challenging Concepts in Urological Surgery
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Discussion
Surgical resection via partial or radical nephrectomy for oncocytomas is considered
curative. When any surgical management strategy is being considered, there are additional patient, disease, and operative factors that all require consideration. So, by
the nature of individuals, surgical resection may not be the strategy of choice for
everyone. This discussion with the patient will be informed by the diagnostics, and of
key concern for oncocytomas, cross- sectional imaging in the form of CT and possible
percutaneous biopsy of the lesion are the mainstay.
Diagnostic imaging
CT imaging is the modality of choice for diagnosis, with magnetic resonance imaging (MRI) being reserved for situations where CT is contraindicated. The dilemma
and indeed the challenge, is that radiographic features of oncocytomas are similar
to that of RCC, making a positive radiological diagnosis particularly difficult. The
classical CT description of an oncocytoma would be a well- defined, usually homogeneously enhancing mass, typically with the presence of a central spoke or stellate
scar, but this can be mimicked by necrosis in RCC, and is not considered specific or
pathognomonic.
sions that show enhancement and washout as hypoenhancement in the nephrogenic
phase, further clouding the waters.12 The use of standard magnetic resonance imaging has also been assessed for distinguishing oncocytomas from RCCs; however,
similar hurdles are encountered with regard to the degree of overlap in radiological
features between the two conditions.13 Specifically, oncocytomas are usually intermediate to high signal on T2- weighted imaging with similar post- contrast findings as CT.14 A recent study looking at MRI characteristics of oncocytomas verses
chromophobe RCCs concluded that the signal intensity following contrast was
higher in oncocytomas as well as the relative wash- in of contrast and could be
used as a discriminatory marker, though the authors state that further research is
required in this area.
Newer techniques may help in the differentiation of oncocytomas from RCCs,
although to date none have been incorporated into standard practice. A recent
meta- analysis of technetium- 99m sestamibi single- photon emission computed tomography/ CT concluded that the technique had a high sensitivity and specificity for
characterizing benign and low- grade lesions, and while this may improve confidence
when recommending active surveillance, the authors did not go as far as suggesting
patients could be discharged from imaging follow- up.16 Work has also recently been
forthcoming regarding the role of mass spectrometry imaging to allow discrimination of renal oncocytoma from RCC subtypes. Mass spectrometry imaging has been
used to study the metabolic and lipid profiles of various renal tissues including renal
oncocytoma, RCC, and normal renal tissue.17 Of note, the authors reported renal
oncocytoma and chromophobe RCC, which present the most significant morphological overlap, were investigated and predictive modelling yielded 100% accuracy in
discriminating these tumour subtypes.17 But again, this has not yet been incorporated
into standard practice, and is to date experimental, but shows potential for application to the clinical setting.
10,11
Additionally, RCCs and oncocytomas are both hypervascular le-
15
Expert comment CT characterization of a renal mass
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CT characterization of a renal mass may suggest the diagnosis of on oncocytoma; however, there
are currently no features which are diagnostic, with considerable overlap with malignant lesions.
A number of methods may in the future provide a more definite diagnosis. Until that point, the
management of oncocytomas must assume a malignant risk and incudes resection, biopsy, and
surveillance. If surveillance is chosen (either with or without biopsy), then imaging intervals should
follow local protocols as for the surveillance of malignant renal lesions. If the mass can be accurately
measured using ultrasound, this may be used for follow- up, otherwise patients will require CT or MRI.
75Case 7 Oncocytoma
Percutaneous biopsy
The role of renal mass biopsy for cases of radiologically suspected oncocytoma has been
much debated. The ability to accurately diagnose oncocytoma versus the more sinister
RCC negates the unnecessary risk of losing part or all of a renal unit, to treat what is a
benign condition. However, the converse is also true. Surveillance based on biopsy results
risks delaying treatment of an RCC if the biopsy specimen provides a false negative. A recent systematic review and meta- analysis examined this issue. It found that one in three
renal biopsies suggesting oncocytoma were ultimately incorrect when the final histology
of nephrectomy specimens was reviewed, and that one in four will actually have RCC.18
Surgical pathology of suspected oncocytomas revealed chromophobe RCC was the most
prevalent variant. The authors concluded that biopsy of a renal mass was found to be
unreliable in confidently diagnosing oncocytoma.18 There is another concern surrounding
the role of renal mass biopsy in the accurate diagnosis of oncocytoma. Whether a preoperative renal biopsy provides a representative sample of the mass lesion must be taken
into account. The existence of hybrid tumours, a scenario where oncocytomas and RCC
coexist, has been described, with an incidence of between 2% and 32%.19 The differential diagnosis usually includes chromophobe RCC (eosinophilic variant) and clear cell
RCC (with granular cytoplasm). If necrosis is present, if there is an increased mitotic rate
or atypical mitotic figures are identified, if spindle or clear cells are seen, the diagnosis
of oncocytoma should be strongly reconsidered. A panel of immunohistochemistry can
be helpful including CK7, vimentin, CD10, RCC, and CD117. The most useful of these is
CK7 where the typical pattern of staining in oncocytoma is focal patchy strong positivity.
Differentiating malignant eosinophilic renal tumours from benign oncocytomas is fraught
with challenges, and often relies on immunohistochemistry, in addition to morphology
from the operative specimen, for the most reliable diagnosis.
3,20
Learning point Surveillance and follow- up
Although oncocytomas are benign in nature, there have been reports of oncocytic cells invading
fat21 and even associated vascular structures, including the renal vein.22 It is, however, extremely rare
that oncocytomas are associated with metastatic spread.23 For those patients that opt for the nonoperative approach, follow- up with some form of surveillance is an important consideration. There are
rare reports in the literature of malignant transformation of oncocytomas, and the more common risk
of progression to chronic kidney disease.
The natural history of oncocytomas is still poorly understood. There has been limited work to assess
this, but the suggestion from one small series was that the natural evolution of an oncocytoma was to
increase in size.25 The authors identified two key markers that they used as indications for surgery. These
were the initial tumour volume and the velocity by which this volume increased over time.25 Despite
this, there is certainly no evidence- based consensus as to what a surveillance programme should look
like, or what the trigger points used to switch from surveillance to surgical intervention may be.
24
76 Challenging Concepts in Urological Surgery
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Expert comment Surveillance
The relative minority of patients who embark on surveillance of their suspected oncocytoma upfront,
would reasonably have a biopsy of the lesion from the outset, notable by the absence of an RCC
subtype in the specimen. Although no strict evidence base exists, a reasonable surveillance protocol
in this cohort may look like a 6- month USS, followed by annual USS imaging. Patient symptoms, size
increase of the lesion, and patient choice would act as triggers for intervention.
A final word from the expert
In 2022, the original decision- making difficulties first identified in 1942 with these renal
lesions has not diminished, and is perhaps more pronounced as the emergence of
incidentalomas with cross- sectional imaging has become established. Adjuncts such as
percutaneous biopsy, CT imaging, and immunohistochemistry act as an aid to inform both
clinician and patient and therefore guide management strategies. When a plan for surgical
treatment has been made, partial nephrectomy should always be considered where feasible.
Patients with suspected oncocytomas are often young, and the removal of an entire renal
unit should be carefully considered and avoided where possible, given the propensity
for development of chronic kidney disease later in life. This carries with it significant
cardiovascular risk and associated morbidity and mortality, as a result of treating what is
thought to be a benign condition. The extent to which patients are able to proportionately
weigh up these longer- term risks associated with nephrectomy against the renal lesion on
the CT scan in front of them is unclear. For those individuals who are under surveillance for
their suspected oncocytoma, local protocols will dictate the frequency and modality of such
follow- up. We know that there is user variability associated with USS imaging, but repeated
CT scans add an additional cumulative risk of radiation exposure in what has already been
discussed as an often- younger cohort of patients. Urologists will continue to be faced
with the diagnostic dilemma of correctly discerning a renal lesion as an oncocytoma with
confidence, as opposed to the more sinister RCC. This point represents the cornerstone in
the management of this benign condition.
References
1. Zippel L. Zur Kenntinis der Oncocyten. Virchow Arch Path Anat. 1942;308:360– 382.
2. Klein MJ, Valensi QJ. Proximal tubular adenoma of kidney with so called oncocytic
features. A clinicopathologic study of 13 cases of a rarely reported neoplasm. Cancer.
1976;38(2):906– 914.
3. Perez- Ordonez B, Hamed G, Campbell S, et al. Renal oncocytoma: a clinicopathologic study
of 70 cases. Am J Surg Pathol. 1997;21(8):871– 883.
4. Amin MB, Crotty TB, Tickoo SK, Farrow GM. Renal oncocytoma: a reappraisal of
morphologic features with clinicopathologic findings in 80 cases. Am J Surg Pathol.
1997;21(1):1– 12.
5. Lieber MM. Renal oncocytoma. Urol Clin North Am. 1993;20(2):355– 359.
6. Ponholzer A, Reiter WJ, Maier U. Organ sparing surgery for giant bilateral renal
oncocytoma. J Urol. 2002;168(6):2531– 2532.
7. Zerban H, Nogueira E, Riedasch G, et al. Renal oncocytoma: origin from the collecting duct.
Virchows Arch B Cell Pathol Incl Mol Pathol. 1987;52(5):375– 387.
8. Nogueira E, Bannasch P. Cellular origin of rat renal oncocytoma. Lab Invest.
1988;59(3):337– 343.
9. Kuroda N, Tanaka A, Ohe C, et al. Review of renal oncocytosis (multiple oncocytic
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lesions) with focus on clinical and pathobiological aspects. Histol Histopathol.
2012;27(11):1407– 1412.
10. Davidson AJ, Hayes WS, Hartman DS, et al. Renal oncocytoma and carcinoma: failure of
differentiation with CT. Radiology. 1993;186(3):693– 696.
11. Hilton S. Imaging of renal cell carcinoma. Semin Oncol. 2000;27(2):150– 159.
12. Paño B, Macías N, Salvador R, et al. Usefulness of MDCT to differentiate between renal cell
carcinoma and oncocytoma: development of a predictive model. AJR. 2016;206(4):764– 774.
13. Pretorius ES, Siegelman ES, Ramchandani P, et al. Renal neoplasms amenable to partial
nephrectomy: MR imaging. Radiology. 1999;212(1):28– 34.
14. Kay F, Pedrosa I. Imaging of solid renal masses. Urol Clin North Am. 201845(3):311– 330.
15. Akin I, Altay C, Guler E, et al. Discrimination of oncocytoma and chromophobe renal cell
carcinoma using MRI. Diagn Interv Radiol. 2019;25(1):5– 13.
16. Wilson M, Katlariwala P, Murad MH, et al. Diagnostic accuracy of 99mTc- sestamibi SPECT/
CT for detecting renal oncocytomas and other benign renal lesions: a systematic review and
meta- analysis. Abdom Radiol (NY). 2020;45(8):2532– 2541.
17. Zhang J, Li SQ, Lin JQ, et al. Mass spectrometry imaging enables discrimination of renal
oncocytoma from renal cell cancer subtypes and normal kidney tissues. Cancer Res.
2020;80(4):689– 698.
18. Patel HD, Druskin SC, Rowe SP, et al. Surgical histopathology for suspected oncocytoma on
renal mass biopsy: a systematic review and meta- analysis. BJU Int. 2017;119(5):661– 666.
19. Haifler M, Copel L, Sandbank J, et al. Renal oncocytoma— are there sufficient grounds
to consider surveillance following prenephrectomy histologic diagnosis. Urol Oncol.
2012;30(4):362– 368.
20. Gorin MA, Rowe SP, Allaf ME. Oncocytic neoplasm on renal mass biopsy: a diagnostic conundrum. Oncology. 2016;30(5):426– 435.
21. Williamson SR. Renal oncocytoma with perinephric fat invasion. Int J Surg Pathol.
2016;24(7):625– 626.
22. Hes O, Michal M, Sima R, et al. Renal oncocytoma with and without intravascular extension
into the branches of renal vein have the same morphological, immunohistochemical and
genetic features. Virchows Arch. 2008;452(3):285– 293.
23. Decet CB, Bostwick DG, Blute ML, et al. Renal oncocytoma: multifocality, bilateralism,
metachronous tumour development and coexistent renal cell carcinoma. J Urol.
1999;162(1):40– 42.
24. National Comprehensive Cancer Network. NCCN guideline with NCCN evidence blocks—
kidney cancer. Version 3.2019. National Comprehensive Cancer Network. 2019. https://
www.nccn.org/ guidelines/ guidelines- with- evidence- blocks
25. Neuzillet Y, Lechevallier E, Andrew M, et al. Follow- up of renal oncocytoma diagnosed by
percutaneous tumor biopsy. Urology. 2005;66(6):1181– 1185.
77Case 7 Oncocytoma
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https://t.me/med1917
SECTION 4
Prostate cancer
Case 8 Localized prostate cancer
Case 9 Oligometastatic prostate cancer
Case 10 Newly diagnosed metastatic prostate cancer
https://t.me/med1917
8
https://t.me/med1917
CASE
Localized prostate cancer
Omer Altan and Alastair Lamb
Expert commentary Freddie C. Hamdy
Case history
A 60- year- old scientist was referred for a urology consultation by his general practitioner on the prostate cancer diagnostic pathway with a persistently elevated serum
prostate- specific antigen (PSA) value of 5.35 ng/ mL and 7.98 ng/ mL on two successive
measurements. This was precipitated by a history of haematospermia and symptoms
of prostatitis, which settled after antibiotic treatment, but the post- treatment PSA value
remained persistently high.
He had a past medical history of type 1 diabetes, arthritis, hypertension, and was
taking naproxen, valsartan, statins, and omeprazole. He had no past surgical history.
He was otherwise fit and active with moderate to good erectile function. Clinical examination was unremarkable, while digital rectal examination revealed a mildly enlarged
benign- feeling prostate with a left- sided firm nodule towards the apex, raising the
suspicion of prostate cancer. The patient was counselled about the significance of the
raised PSA and suspicious digital rectal examination and the need to investigate him
further with a prostate multiparametric magnetic resonance imaging (mpMRI) scan
and prostate biopsy.
Clinical tip Initial assessment
● The patient should be made aware early in the diagnostic pathway about the clinical suspicion of
prostate cancer.
● The patient needs to be informed about the most common risks of prostate biopsy, whether
transrectal ultrasound (TRUS) guided or using the transperineal approach— risks include haematuria,
acute urinary retention, and sepsis.
● If available, consider offering local anaesthetic transperineal (LATP) biopsy for improved targeting
of visible lesions on imaging, particularly in the anterior region of the prostate, improved systematic
sampling, and probable reduction in sepsis.
● It is important to document whether the patient had a previous history of antibiotic use for urinary
tract infections or other conditions which required quinolones (previous TRUS biopsy), as his
colonic flora might have become resistant to quinolones which are commonly used for urinary tract
infection prophylaxis pre and post TRUS biopsy.
● A voiding cystometry should be performed prior to prostate biopsy to obtain baseline voiding
pattern information. This is one of the essential eligibility criteria for brachytherapy if the diagnosis
of prostate cancer is confirmed (threshold Qmax 12 mL/ s or higher).
● Erectile function prior to biopsy should be documented, which will be useful to plan treatment as
necessary, ideally using validated questionnaires (e.g. International Index of Erectile Function).
● Offer pre- biopsy imaging in the form of mpMRI or biparametric MRI of the prostate, with
interpretation based on the Prostate Imaging Reporting and Data System (PI- RADS) (or Likert)
classification from 1 to 5.
8–10
1– 3
4– 7
82 Challenging Concepts in Urological Surgery
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Figure 8.1 Multiparametric magnetic resonance imaging (mpMRI) of the prostate. Coronal and axial T2
weighted (a, b), axial apparent diffusion coefficient (c), and high B- value (d) parameters.
The patient underwent a mpMRI scan of his prostate (Figure 8.1). The prostate
volume was 26 cc and there was a 21 mm area of decreased T2 signal within the left
peripheral zone posterolaterally, in the mid- portion of the gland, showing restricted
diffusion and early enhancement, classified as PI- RADS 5 lesion. There was also
broad capsular abutment.
The patient was offered TRUS- guided targeted and systematic biopsies
(Table 8.1).
Table 8.1 Biopsy results
Left Right
Cores and Gleason Grade
Group (GGG)
Tissue involvement 90% 40%
Maximum core length 16 mm (100% of core) 11 mm (60% of core)
Perineural invasion Yes No
Extraprostatic extension No No
Lymphovascular invasion No No
Bilateral adenocarcinoma, maximum Gleason 7 (4 + 3), Grade Group 3.
5 of 5 cores positive for GGG3
(Gleason 4 + 3 = 7)
5 of 5 cores positive for GGG2
(Gleason 3 + 4 = 7)
Learning point PI- RADS
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PI- RADS version 2 classification is a scoring system for mpMRI of the prostate which indicates the
likelihood of a lesion to represent significant prostate cancer. This is based on the assessment of
T2- weighted, diffusion- weighted, and dynamic contrast enhancement imaging. Based on these, a
score of 1– 5 is given to each lesion. PI- RADS 1– 2 lesions are low risk that are unlikely to represent
serious disease, PI- RADS 3 lesions are considered equivocal, while PI- RADS 4– 5 lesions are considered
suspicious and more likely to reveal cancer at the moment of prostate biopsy. The Likert system for
scoring is similar but represents a sequential grading of risk from 1 to 5. Interpretation of the mpMRI
can be challenging in younger men.
9,10
MRI is a useful tool for local staging and can help preoperative
planning should the patient require radical surgery, particularly to determine the appropriateness and
risks of neurovascular bundle (NVB) sparing.
An MRI description of ‘capsular abutment’ can sometimes indicate a higher risk of capsular and
extracapsular involvement and locally advanced prostate cancer (T3a disease).11 If the MRI shows
a PI- RADS 1– 2 abnormality, the patient can be counselled towards expectant management as the
likelihood of finding clinically significant prostate cancer is low, approximately 5– 15% regardless of
PSA density.
According to the Prostate MRI Imaging Study (PROMIS) trials, up to 27% of patients could avoid
prostate biopsies.
12
13
If the clinical suspicion of disease outside visible abnormalities is high, then the patient should be
offered systematic TRUS or LATP.
Learning point Biopsy approaches
● Transrectal biopsies, although widely available in most units carry the disadvantage of a sepsis rate
of up to 5%.
● Performing MRI cognitive or fusion prostate biopsies have a similar diagnostic yield for clinically
significant prostate cancer.
2
19
● TRUS biopsy has a lower detection rate compared to MRI- targeted biopsies for clinically significant
prostate cancer and a higher detection rate for clinically insignificant prostate cancer according to
the Prostate Evaluation for Clinically Important Disease: Sampling Using Image Guidance or Not?
(PRECISION) trial.
13,14
● Other studies have shown that when performing MRI- targeted biopsies only, there is a risk for
missing clinically significant prostate cancer, concluding that both systematic and targeted biopsies
should be performed.
12
Given the predominance of Gleason pattern 4 disease, the patient received an MRI
of his bone marrow which was negative for metastatic bone disease. The patient’s
prostate cancer was categorized as high- volume, intermediate- risk disease, cT2cN0M0,
with a risk of extracapsular extension on the left side of the prostate, based on radiological and digital rectal examination findings.
The patient was counselled in parallel consultations by the urologist and clinical
oncologist (radiation oncologist) and offered different forms of radical treatment as
either surgery, in the form of laparoscopic robot- assisted radical prostatectomy (RARP)
and extended pelvic lymph node dissection (PLND), or neoadjuvant androgen deprivation therapy followed by external beam radiotherapy.
The patient’s choice was to receive a RARP. He expressed a particular preference for
bilateral NVB sparing, despite the fact that during the initial surgical consultation he was
advised that in view of the findings, the approach recommended would be to receive
a RARP with wide excision of the NVB on the left side and a nerve- sparing procedure
83Case 8 Localized prostate cancer
Expert comment Additional
systematic biopsies
In the presence of an mpMRIvisible lesion, targeted biopsies
should be performed14 and
we would advocate additional
systematic biopsies due to the
approximately 30% rate of nontarget clinically significant prostate
cancer detection and to aid
planning of radical treatment.
It is sensible, for data auditing
purposes, to send these separately
for histopathological analysis.
Expert comment LATP
LATP prostate biopsies could be a
good alternative to TRUS prostate
biopsies. They may have superior
diagnostic accuracy but lower risk
of urinary sepsis with equivalent
patient tolerability.5 A randomised
trial to answer this question
(TRANSLATE Trial; NIHR131233)
began across several sites in the UK
in early 2022.
5,15– 18
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