Prostate biopsy

The number and fraction of positive biopsies are used to risk stratify patients with prostate cancer,15 so it is important to accurately record the number of biopsies submitted for histological examination. Pathologists may overestimate the number of biopsies (positive and total) due to fragmentation of the needle cores so the operator should indicate the number of biopsies submitted in each container.

It is useful to record the macroscopic lengths of the submitted cores as a quality control indicator. Short macroscopic lengths could indicate a suboptimal biopsy technique while significant discrepancy between the macroscopic and microscopic core lengths would suggest tissue loss during histopathological processing.

It can be challenging to embed prostate biopsies flat, particularly when multiple cores are submitted in a cassette. Therefore, it is recommended that no more than three cores should be submitted per cassette.17 However, it would be reasonable to submit more cores in a cassette if the cores are embedded flat and their entire lengths examined. Submission of multiple cores in a cassette could be facilitated by use of multiplex chips that could reduce tissue handling and core fragmentation.18

Transurethral resection of prostate

The weight of transurethral resection of prostate (TURP) specimens should be recorded because sampling protocols are based on specimen weight. A commonly recommended protocol is to submit all tissue up to 12 g and then one cassette for every additional 5 g of remaining tissue, which would amount to about 10 blocks from a 25 g TURP specimen.6 7 The clinical utility of such extensive sampling in patients with no clinical suspicion of prostate cancer has been questioned; a few blocks would be sufficient to detect tumours that are large enough to cause urinary retention.19 It has been suggested that current sampling protocols that are specifically designed to detect occult prostate cancer could amount to histological screening for prostate cancer without proper informed consent.20

If <5% of the chips are involved by prostate cancer (stage category T1a) then it is suggested that the rest of the tissue could be submitted for more accurate estimation of tumour extent.7 It is important to appreciate that such recommendations were designed in the pre-MRI era. In contemporary practice, pathological assessment of tumour extent is less important as patients with T1a prostate cancer would often be assessed with serum PSA and MRI.

Considering the above concerns, we feel that the current recommendations for TURP sampling need to be reconsidered.

Macroscopic description of prostatic chips is generally of limited clinical value, but it would be good practice to submit any macroscopically different chips for histological examination.

Enucleations/open (simple) prostatectomy

Simple prostatectomy is performed to relieve refractory urinary obstruction in patients with large clinically benign prostate glands. This procedure has become less common with the advent of other medical and surgical interventions, so such specimens are rarely encountered in developed countries.

The overall weight of such specimens that are generally submitted as multiple nodular pieces should be recorded. It is, however, not necessary to ink the specimen or to record the sizes of individual nodules. There are no evidence-based guidelines for sampling such specimens; a weight-based sampling protocol akin to TURPs is generally suggested.

As with TURPs, any area that appears macroscopically different should be sampled.

Radical prostatectomy

Meticulous macroscopic examination is less important in radical prostatectomy specimens if these are completely submitted for histological examination. Specimen size and dimensions are also of limited clinical utility. Specimen weight has been shown to be a simpler and more reproducible indicator of specimen size.21 Prostatic weight should be measured without the seminal vesicles as the latter could significantly affect the recorded weight, particularly if the gland is relatively small.

The right and left halves of the prostate should be inked with different colours before slicing to facilitate reporting of the location of extraprostatic extension and margin positivity. The specimen should be handled with care and sliced only after it is properly fixed as the gland has only a thin rim of connective tissue that can be easily disrupted leading to ‘false positive’ margins (figure 1). Any clips and staples attached to the specimen should be removed with care to avoid disrupting the surface and resection margin. Surface disruption could also occur if in vitro needle biopsies are taken to obtain fresh tissue. If macroscopic disruption is identified, then that area should be inked using a different colour.

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Figure 1

Irregular flaps of tissue on the surface of a robotic radical prostatectomy specimen may be due to intraoperative tissue disruption. Tumour at the inked specimen margin (arrow) could be misinterpreted as a positive resection margin if the tissue flap is not represented in the examined plane of section. (A: low power, B: high power of boxed area in A).

The apical and base margins should be submitted as radial sections.

Renal tumour biopsy

Radiologically indeterminate renal masses may be biopsied to guide decisions regarding patient management, especially in cases with widespread metastasis or if a conservative management like a radioablation or active surveillance of the small renal mass is being planned. Establishing a diagnosis in such limited material can be challenging and may require use of immunohistochemical panels or molecular testing so every effort must be made to conserve tissue during processing. Submitting the needle cores in separate cassettes could reduce tissue loss and provide more unstained sections for ancillary testing.

Radical nephrectomy

Scrupulous macroscopic evaluation of radical nephrectomy specimens is critical for accurate diagnosis and risk stratification of renal tumours. The dissector should be aware of preoperative radiological findings and operative findings as these can assist macroscopic assessment of the specimen.

The specimen should be promptly sliced into on receipt in the laboratory to facilitate fixation. Suboptimal fixation can adversely affect histological examination as well as ancillary immunohistochemical and molecular testing. Most patients with renal cancer do not require adjuvant therapy and such treatment cannot be commenced until the patient has recovered from the major surgical procedure, so a short turnaround time for reporting radical nephrectomy specimens is not critical. The specimen should, therefore, be properly fixed before definitive thin slicing to optimise the collection of critical prognostic and predictive data. Thin slicing is necessary for detection of focal abnormalities such as invasion of the renal sinus, renal vein or perinephric fat.

Maximum tumour dimension is a critical parameter for staging organ-confined renal cell carcinoma (RCC) and should be accurately recorded. Tumour size measurement should include any extrarenal extension, but intravascular tumour should be excluded.22 If the maximum dimension in the sliced plane appears significantly lower than the radiologically reported tumour size then the third dimension (perpendicular to the plane of section) should be measured, particularly around clinically critical thresholds such as 4 cm, 7 cm and 10 cm. However, only the largest tumour dimension needs to be routinely recorded as other dimensions generally have no clinical utility.

If the kidney contains multiple grossly similar tumours, then the eighth edition of the American Joint Commission on Cancer tumor-node-metastasis (TNM) classification recommends recording the maximum dimensions of up to five tumours and using the largest measurement to assign the pT category.22 Any tumour that appears grossly different should be measured as tumours with different histologies would require separate staging.22

Rarely, a unilocular smooth walled cyst containing a solid nodule may be encountered. In this scenario, the maximum dimensions of both the cyst and the nodule should be separately recorded as the latter may represent an RCC arising in a benign cortical cyst, which would be staged based on the size of the solid mass.10

In contrast, specimen dimensions are of little clinical utility and do not need to be routinely reported.

It is important to document specimen components, particularly the presence or absence of the adrenal gland. If the adrenal gland was included in the radical nephrectomy, then a subsequent ipsilateral suprarenal mass is unlikely to represent an adrenal tumour. In contemporary surgical practice, the adrenal gland is not routinely excised during a radical nephrectomy so it would be helpful if the urologist indicates in the request form when the adrenal gland has been preserved.

The cut surface of the tumour should be carefully evaluated to identify and sample focal changes. It is particularly important to recognise solid fleshy white areas in a renal tumour that could represent sarcomatoid change, which would dramatically worsen the prognosis in an otherwise low-risk RCC. Histological determination of the extent of sarcomatoid change that has been reported to be prognostically significant would be subject to sampling bias as it would be affected by the proportion of sections taken from the aforementioned solid fleshy white areas. It would, therefore, be prudent to record a rough estimate of the macroscopic extent of possible sarcomatoid differentiation. Tumour necrosis is an important prognostic factor in clear cell RCC so it is important to grossly identify and sample any areas of necrosis.23 It is recommended that the histological percentage of necrosis could be reported23 but as with sarcomatoid change this would be subject to sampling bias.

It is important to record the location of the tumour within the kidney. A central location would suggest the possibility of urothelial carcinoma or collecting duct carcinoma. A brief description of the tumour’s appearance is often useful. A variegated, solid and cystic cut surface with yellow, grey and brown areas is characteristic of clear cell RCC, while a solid firm grey-white appearance is typically seen in urothelial carcinoma and collecting duct carcinoma. Although a central stellate scar is characteristic of oncocytoma, it may also be seen in other slow growing renal tumours such as chromophobe RCC and low-grade clear cell RCC. It is also important to document tumour multifocality. Macrophotography would be useful for documenting macroscopic appearances, particularly when these are unusual.

Accurate identification of renal vein, sinus fat and perinephric fat invasion are important as these are often critical for pT stage categorisation.22 These parameters would, however, be of limited significance in patients with clinical, radiological or macroscopic evidence of either inferior vena cava (IVC) invasion or metastatic disease so detailed examination and extensive sampling would not be necessary in these scenarios.

In earlier versions of the TNM classifications, renal vein invasion had to be grossly evident to be categorised as pT3a, but this requirement was removed in the eighth edition (2016).22 Particular attention should be paid to the interface between the tumour and the renal sinus with any area deviating from the rounded tumour contour sampled to detect vascular or renal sinus invasion.10 Current evidence suggests that involvement of the renal sinus is more predictive of adverse outcome than peripheral perinephric fat invasion.23 The tumour–sinus interface should be generously sampled, particularly in larger tumours as clear cell RCCs that are over 7 cm in maximum dimension (pT2 at least) are almost always associated with sinus invasion. It has recently been suggested that the TNM staging system could be modified to incorporate all >7 cm clear cell RCCs into pT3a category, thereby removing the need to extensively sample the tumour–sinus interface of such tumours.24 Apparent multifocality of clear cell RCC often represents intravascular extension due to retrograde venous spread of tumour. The periphery of such nodules should be sampled to facilitate identification of the venous wall. The specimen should be carefully examined for renal vein invasion but probing of the venous system that could result in tumour thrombus dislodgement is discouraged. The renal vein margin status should be reported as it could predict local tumour recurrence. Tumour extending into the IVC is often ‘milked’ back into the renal vein and may pop back out of the incised renal vein margin. The margin of the vein as opposed to that of the intravascular tumour should be sampled and renal vein margin positivity reported only if the tumour is adherent to, or invading, the vessel wall in this section. If IVC thrombus is submitted separately then the periphery of the specimen should be sampled to identify mural invasion that would amount to pT3c. Sampling to detect IVC wall invasion is challenging when the thrombus is removed piecemeal.

Perinephric fat invasion may be subtle, as when composed of nodules that bulge out into the plane of the fat. Megablocks could help clarify the relationship of the tumour and perinephric fat as this may not be apparent in smaller sections from the interface of the tumour and perinephric fat.

If the ipsilateral adrenal gland is involved by tumour, then it is important to document whether this involvement is continuous (pT4) or discontinuous (pM1). This distinction is a macroscopic assessment that is subsequently confirmed by histological examination.

Extension of RCC into the pelvicalyceal system is rare but should be documented if identified because it is categorised as pT3a in TNM 8.22 The pelvicalyceal system and ureter should also be carefully examined to exclude coexisting urothelial neoplasia.

Tumour extension beyond the Gerota’s fascia (pT4) is rarely encountered as such tumours are generally inoperable. It is recommended that tumour involving the perinephric margin should be reported as extending to the Gerota’s fascia (pT4).10 It may be helpful to selectively ink tumour at the specimen surface to facilitate microscopic confirmation of this finding.

The hilar fat should also be carefully examined for lymph nodes that should be submitted for histological examination.

Finally, the background kidney should be examined for any coexisting pathology and a section away from the tumour submitted to enable identification of any underlying renal pathology.

Partial nephrectomy

Specimen dimensions of partial nephrectomy specimens should be recorded as these could provide an estimate of the amount of renal parenchyma that has been resected. Tumour features should be assessed as described above in radical nephrectomies. However, partial nephrectomy specimens would not include the renal vein and rarely contain significant amount of renal sinus tissue so tumour involvement of the renal vein and renal sinus generally cannot be assessed in these specimens.

The renal parenchymal margin must be inked, and the nearest margin identified after thin slicing should be sampled. Background kidney should also be sampled. However, there is often scant normal renal parenchyma in these specimens so it may not be possible to sample renal tissue away from the tumour.

Radical orchidectomy

The pathologist must be aware of the preoperative serological and radiological findings prior to sampling orchidectomy specimens. A significantly raised serum alpha-fetoprotein (AFP) level would suggest a non-seminomatous germ cell tumour (GCT) and such patients would generally be managed as a non-seminoma even if the pathological diagnosis is pure seminoma.16 In this scenario, extensive sampling of the tumour to identify a non-seminomatous component may not be necessary while generous sampling of the peritumoural tissue to detect vascular invasion would have greater clinical utility. Radiology findings could help localise a small, generally incidentally detected tumour that was not evident on bivalving the orchidectomy specimen.

The orchidectomy specimen must be promptly sliced on receipt in the laboratory to facilitate fixation because the thick testicular capsule would hinder formalin permeation. Slicing should be performed by bivalving the specimen from lateral aspect towards the hilum to allow proper assessment of rete testis, epididymis and hilar soft tissue. Prompt fixation is critical for accurate morphological and immunohistochemical assessment of testicular tumours. Surgeons could be trained to bivalve these specimens before placing them in formalin in scenarios where delays in delivering the specimen to the laboratory are expected, such as a long weekend. Slicing of fresh specimens could result in bulging of the cut surface and potential ‘pseudovascular invasion’ due to artifactual spread of friable tumour into vascular spaces but these are less important than compromised tumour typing due to poor tissue preservation. The risk of reporting ‘pseudovascular invasion’ can be reduced by not sampling the cut surface resulting from the initial slicing of the fresh specimen. The spermatic cord margin could be sampled before slicing the orchidectomy specimen to preclude contamination by friable tumour.

It is generally recommended that the dimensions of testis, the length of spermatic cord and tumour location should be reported12 but these are of limited clinical utility. The maximum dimension of the tumour must be recorded as it could guide patient management, particularly in stage I seminoma.

The tumour should be thinly sliced, and any macroscopically distinct area sampled as this may represent a different component with prognostic and therapeutic implications. It is important to sample cystic, necrotic and haemorrhagic areas in a seminoma to detect a minor non-seminomatous component, particularly in patients with a normal serum AFP. In contrast, identification of a seminomatous component in a non-seminomatous tumour is generally of little clinical significance. As noted previously, if the serological findings or macroscopic appearances are suggestive of non-seminoma then the tumour-testis interface should be generously sampled to detect vascular invasion, which could trigger adjuvant chemotherapy.

Rete testis stromal invasion is an adverse prognostic factor in seminoma (but not non-seminoma) so it is particularly important to sample the rete testis in pure seminoma.

Accurate staging of testicular GCTs requires careful macroscopic examination. If the spermatic cord is involved by tumour, then it is important to record its relationship with the testicular tumour. Analogous to adrenal involvement by RCC, a discontinuous tumour deposit in the spermatic cord would be staged as pM1 while direct extension of a testicular tumour would be pT3.22

TNM 8 defines the spermatic cord as being superior to the level of the head of the epididymis.22 The distinction of spermatic cord invasion (pT3) from epididymal invasion (pT2) is, therefore, based on macroscopic assessment. The spermatic cord just superior to the head of the epididymis should be sampled and soft tissue deposit in this block interpreted as direct spermatic cord invasion.

Partial orchidectomy

Macroscopic examination and tumour sampling would be largely similar to that in radical orchidectomy specimens, but it is also important to report the completeness of excision in partial orchidectomies. The latter specimens should therefore be inked, the macroscopic distance of tumour from the specimen margin recorded and the nearest margin sampled.

Retroperitoneal lymph node dissection

Pathology findings in retroperitoneal lymph node dissection (RPLNDs) performed for residual retroperitoneal masses after chemotherapy for GCTs would guide subsequent patient management.25 Aggressive second line chemotherapy may be indicated if a viable non-teratomatous malignant germ cell component is identified. Completeness of surgical resection is critical in residual teratoma and somatic malignancy arising in a teratoma as these would not respond to GCT chemotherapy.

RPLND specimens must be handled very differently from other lymph nodal block dissections. These specimens should be inked and the distance of any residual tumour from the nearest margin recorded. Grossly involved lymph nodes should ideally be entirely submitted when feasible. If complete submission is impractical, careful macroscopic examination and sampling of any different appearing focus is required. It is also important to sample areas of necrosis.

Cystectomy/cystoprostatectomy/anterior exenteration

Cystectomy specimens should be promptly inflated with formalin either in the operating theatre or on receipt in the laboratory to stretch out the mucosa and facilitate macroscopic examination. The specimen components should be documented but specimen dimensions do not have to be recorded as they have little clinical utility. Routine inking of the specimen is not recommended as ink would seep into the fat hindering identification of perivesical lymph nodes. Selective inking of the specimen margin close to extravesical tumour is sufficient.

Before slicing the specimen, the pathologist must be aware of relevant clinical and radiological information such as the indication for the surgery, tumour location, history of neoadjuvant therapy and radiological evidence of extravesical extension or prostate cancer. For example, sampling could be limited if cystectomy was performed as a palliative procedure or targeted to the site(s) of radiological extravesical extension or prostatic involvement. If no tumour or TURBT site is seen in the postneoadjuvant chemotherapy scenario, then sampling could be targeted at the tumour location as recorded in the patient’s clinical records.

After fixation, the specimen should be thinly sliced and carefully examined for any residual tumour or other mucosal abnormality with sampling focused on macroscopically abnormal areas. It is important to appreciate that less than 0.2% of the specimen (or macroscopically abnormal area) would be histologically examined even if the specimen/abnormal area is completely processed in paraffin blocks since only a 3–5 µm thick section would be examined from each block. Extensive random sampling of macroscopically normal tissue to detect residual microscopic tumour is therefore not required.

The maximum dimension of the grossly visible tumour should be recorded. Sampling of residual tumour should be directed at determining the maximum depth of invasion. If detrusor muscle invasion was identified in the TURBT specimen, documentation of pT2 disease in the cystectomy is less important. It is critical to document any macroscopically identified extravesical extension as this would categorise the tumour as at least stage pT3b.22 In contrast, identification of carcinoma in situ (CIS) in the bladder is generally of limited clinical utility so it is not necessary to extensively sample morphologically normal flat epithelium. It is also important to carefully examine the perivesical fat for lymph nodes and tumour deposits, which should then be sampled.

As noted earlier, residual tumour may not be apparent in postneoadjuvant chemotherapy cystectomy specimens. In this setting, careful macroscopic examination of the bladder by thin slicing followed by sampling of the previous TURBT site and any abnormal appearing area is sufficient. The size of residual tumour has been reported to be prognostically significant in the postneoadjuvant scenario. However, studies have used size cut-points around 3 cm diameter26 that would be grossly visible so extensive sampling of the grossly normal bladder to detect microscopic residual disease is not required.

There is a significant variation in the prostatic sampling protocols in radical cystoprostatectomy specimens with some institutions routinely submitting the entire gland for histological assessment. However, some guidelines such as those from the Royal College of Pathologists6 emphasise that prostatic sampling should be directed at accurately staging the known bladder cancer rather than detection of incidental prostate cancer. It is, therefore, not necessary to extensively sample the prostate gland in patients with no clinical or radiological suspicion of prostate cancer. As with TURP specimens, submitting the entire prostate gland to identify incidental prostate cancer would amount to cancer screening. Finally, detection of incidental prostate cancer in cystoprostatectomy specimens would have little clinical utility as patient outcomes are generally driven by the bladder cancer.27

Prostatic sampling to stage bladder cancer should focus on the base of the gland to identify direct extension of bladder tumour into the prostate, which would amount to pT4 and the periurethral region to detect prostatic stromal invasion by urothelial carcinoma involving the urethra or submucosal prostatic ducts that would be staged as a synchronous urethral carcinoma; pT2 if confined to the prostate gland.22 The bladder–prostate interface does not have to be sampled in cases where tumour had been resected from the dome of the bladder and no tumour is seen at the bladder base.

Cystectomy specimens from females should be sliced in the transverse plane to assess tumour extension into the uterus. When appropriate, sections of the posterior bladder wall in continuity with the anterior uterus should be submitted to evaluate uterine involvement. In the rare cases where the tumour appears close to the vaginal margin, this margin must be sampled.

In the absence of clinical, radiological or overt macroscopic evidence of ureteric tumour, the ureters should be carefully opened with scissors and the mucosal surface carefully examined for any focal abnormality that should be sampled.

Sections of the ureteric and urethral margins should be submitted to detect CIS or invasive tumour at these margins. If segments of the distal ureter are submitted separately, then it is not necessary to submit the ureteric margins from the cystectomy specimen. In contrast to the cone method used to sample the apical margin of radical prostatectomy specimens, the prostatic urethral margin of cystectomy specimens should be sampled as a slightly thicker shave section as the distal prostatic urethra often retracts into the specimen.

Intraoperative frozen section analysis may be used to assess the status of the ureteric and urethral margins as margin positivity has been shown to be associated with higher risk of recurrence.28 However, the risk of local recurrence after cystectomy is quite low and invasive tumour at the specimen margin is generally encountered in high-risk patients who are more likely to develop distant metastasis, which would determine patient outcome so routine frozen section analysis of ureteric margins may not be justified.29 CIS is a field change with skip lesions so there may be residual tumour in the patient even with clear margins.

Nephroureterectomy and ureterectomy

Specimen dimensions are of little clinical utility with the possible exception of the ureteric length in segmental ureterectomy specimens. Maximum tumour dimension and tumour focality (unifocal vs multifocal) are mandatory data items in some guidelines30 because some studies have shown them to be predictive of intravesical recurrence and patient outcome. However, these data items do not dictate patient management and are considered optional in other guidelines.7 Tumour location may be predictive of intravesical recurrence with the risk highest in tumours of the lower ureter and lowest in those located in the renal pelvis.30

Accurate tumour staging is critical in resections of the upper urinary tract as high-stage tumours would be treated with adjuvant chemotherapy. These specimens must, therefore, be thinly sliced and carefully examined to identify and then sample any area of tumour invasion into the renal parenchyma or periureteric soft tissues.

Urethrectomy

The maximum tumour dimension should be reported as it has been shown to be a significant prognostic factor.30 Other tumour dimensions have no clinical significance. It is important to record the location of the tumour within the urethra as proximally located tumours have a worse outcome.30 Tumour location also impacts staging of urethral carcinomas in males as there are different rules for pT subcategorisation of tumours in the prostatic and penile urethra.22

Lymph node block dissections

There are significant differences in TNM rules for pN stage subcategorisation of urothelial carcinomas arising in the urethra, urinary bladder and upper urinary tract,22 which could have implications for macroscopic assessment of nodal dissection specimens. pN subcategorisation of urethral carcinoma is based on number of positive regional nodes; that of bladder carcinoma on the location and number of positive regional nodes; and upper urinary tract carcinoma are staged using the number and size of positive regional nodes. The maximum dimension of a macroscopically involved lymph node is therefore critical in resections for carcinomas of the upper tract while recording the number of positive nodes is crucial in resections for carcinomas of the urethra and bladder.

Location of involved lymph nodes is important for pN subcategorisation of bladder cancer. Common iliac lymph nodes are considered regional nodes for bladder carcinoma so such tumours would be staged as pN3 if these nodes are involved.22 This is in sharp contrast to prostate cancer staging where common iliac lymph nodes are designated as non-regional (pM1 if positive).22

Lymphadenectomy specimens should be carefully examined by palpation and thin slicing, and all identified lymph nodes submitted. It is good practice to record the maximum dimension of grossly involved nodes, particularly if they are too large to be ascertained by microscopic examination, as well as the number of nodes submitted in each cassette. Weight could be used as a simple and reproducible indicator of the size of lymphadenectomy specimen.21

Penile biopsies

Biopsies of the penile skin or mucosal surfaces are more commonly performed in urological, dermatological and sexual health practice for diagnosis. These are usually small superficial incisional specimens and therefore careful macroscopic examination to identify the epidermal or mucosal surface is paramount to allow accurate embedding and sectioning. It is suggested that biopsies less than 3 mm in width are embedded as received with levels performed after examination of an initial H&E to ensure accurate embedding. Specimens greater than 3 mm can be bisected or serially sectioned as is common practice for other sites. However, lesions that are <3 mm maximum dimension should not be bisected as this would risk loss of the entire lesion during ‘facing’ of the paraffin block in the laboratory. Slicing could be performed along the edge of the lesion so that it is entirely in one block, which could be examined in multiple levels for proper visualisation of the lesion.

Foreskins

Circumcisions are a very commonly performed procedure for a variety of benign indications but may harbour incidental neoplasia. Measurements of the specimen are of limited clinical value, however, careful observation of the surface is required to identify any lesions or plaques (firm white areas commonly representing balanitis xerotica obliterans). The foreskin comprises inner mucosa (smooth, shiny) and outer skin (rugose and duller) and these should both be sampled routinely, commonly achieved in a single transverse section, with sampling of any lesions. In adults, circumcision is often surgically accomplished by first performing a dorsal slit before removing the foreskin radially, and therefore, these specimens are often received as a strip or in two pieces. The cut ends of the specimen, if identifiable, are therefore not true resection margins and neither is there a deep margin. Should an incidental neoplastic lesion be detected, the only two true margins are the penile skin and glanular resection margins. However, following fixation, such margins can be difficult to separate from the dorsal slit, especially if the sample was received in two or more pieces and not orientated or pinned out.