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Let’s talk about margins ~ Urology education

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Aims:

  • Discuss and illustrate surgical margins, using radical prostatectomy specimen as an example.
  • Discuss the difference between surgical and pathological margins

Discussion:

General

Surgical margins are a contentious issue and ‘clear margins’ mean different things to a surgeon depending on the organ or disease being treated; in breast cancer, 10 mm is considered clearance while in skin surgery for melanoma 5 to 10 mm is advocated. For the urologist, clear margins can be a wisp of fibrous tissue.

The role of a pathologist
Fig 1 - Microscopic appearance of black ink at margin

Fig 1 - Microscopic appearance of black ink indicating 'pathological' margin

When the specimen is received by the pathologist, the intact specimen is ‘painted’ in an indelible coloured ink. Different colours may be used so that landmarks and therefore orientation can be achieved under the microscope. The inked is allowed to dry before the specimen is cut in an appropriate manner. The ink on the outer aspect of the tissue survives tissue processing and is visible under the microscope during the microscopic assessment of the tissue (Fig 1).

‘Surgical’ vs ‘pathological ‘ margin.

In theory, the ink on the outer surface serves as a marker for the ‘surgical margin‘ but in practice we often define it as the ‘pathological margin‘, the emphasis being that these may not be exactly the same thing.

Using a radical prostatectomy specimen as an example, there are several reasons for this;

Fig 2 - Microscopic photograph of ink at 'false' margin.

Fig 2 - Microscopic photograph of ink at 'false' margin due to disruption of surface adipose tissue. The real margin contour is outlined by the dotted red line. Ink is present on deeper tissue (arrow) but this is not true margin.

  • The true surgical margin of the specimen is sometimes altered during the surgical procedure (tissue disruption secondary to traction) or soon after (eg tissue banking).
  • The nature of the tissue may contribute to interpretation difficulties; adipose tissue is susceptible to disruption between lobules which can allow marking ink to reach well below the true surgical margin (Fig 2).
  • Specimens are rarely removed with a clean uniform margin with the outer surface often undulating. If mechanical cutting is used there are often ‘microcuts’ extending into the specimen, again contributing an an irregular surface. This can result in loss of small fragments of surface tissue during specimen sectioning. (Fig 3a-c).
  • Diathermy alters the tissues to a depth of approximately 1 mm on either side of an excision plane and therefore the pathologist cannot always assess viability of tissue/tumour in this region.
    Fig 1a-b . Macroscopic photograph of prostate speciemn showing irregular surface.

    Fig 1a-b. Macroscopic photograph (before inking) of radical prostatectomy specimen including posterior surface (a) and apical surface (b) showing surface irregularity including small linear 'micro-cuts'.

    Fig 1c - macroscopic photograph of cut section of prostate

    Fig 1c - Macroscopic photograph (after inking) of horizontal section of prostate, showing irregular inked surface outline. There is incidental periurtehral change suggestive of recent TURP.

It is for these reasons that we preferentially use the term ‘pathological margin’.

Other relevant margin features

Continuing on with the prostatectomy specimen as an example, there is no doubt that margin status holds prognostic significance (Swindle et al) but we have progressed beyond the simple “positive or negative” description; it is our practice to describe a positive ‘pathological’ margin with the following features;

  • Location/s, including clarification of whether it is in an area of extraprostatic extension (Chuang et al).
  • Longitudinal measurement (Watson et al)
  • We will often note whether diathermy changes are present at a positive margin as this tumour may not be viable.

Other features that may be noted include;

  • The shape of the positive margin – is it broad and shallow or sharp and deep, which is particularly important in the case of ‘positive in an area of capsular incisions’.
  • A recent paper indicates that Gleason score of the tumour at the margin may be important (Savdie et al).

Although not routinely described, we often report on areas of a prostate where a surgeon has passed into/transected benign prostate, particularly away from the apex; the reason being that the remaining benign viable prostate may explain a post operative PSA measurement, or alternatively the residual prostate tissue may explain ‘recurrent’ tumour development at a later date.

Margins and staging

The staging of a positive margin is also contentious.  The prostate does not have a true capsule and therefore assessing extraprostatic extension can be difficult, particularly at the apex, bladder neck and anterior aspects, where there is no clear point of cleavage between prostate stroma and surrounding tissues. Anterior positive margins are usually associated with large transition zone carcinomas which again particularly involve the bladder neck. Many of these margin positive tumours are pT3 tumours with involvement of the anterior or bladder neck stromal tissue.  If tumour is seen at a margin at the apex surrounded by voluntary muscle, it is usually described as occurring in an area of extraprostatic extension (Epstein et al), although the subjective nature of assessment in these areas may explain lack of concordance in reporting of these factors, even by specialist uropathologists (Evans et al).

Summary

The important points to take away are;

  • A margin needs a lot more description that just ‘positive’ or ‘negative’
  • A ‘surgical’ margin and ‘pathological’ margin’ are not the same; we favour ‘pathological margin’ for the reasons outlined above.
  • Margins assessment is not black and white – some assessment is subjective and there is intraobserver variability, even among expert uropathologists.
  • Whenever you have doubts about a margin don’t hesitate to discuss it with your pathologist.

A/Prof John Pedersen and Dr Andrew Ryan


References

Epstein JI, Amin M, Boccon-Gibod L, et al. Prognostic factors and reporting of prostate carcinoma in radical prostatectomy and pelvic lymphadenectomy specimens. Scandinavian Journal of Urology & Nephrology 2005 – Supplementum 216:34–63.

Swindle P, Eastham JA, Ohori M, et al. Do margins matter? The prognostic significance of positive surgical margins in radical prostatectomy specimens. Journal of Urology (2005) 174(3):903–907.

Watson RB, Civantos F and Soloway MS. Positive surgical margins with radical prostatectomy: detailed pathological analysis and prognosis. Urology (1996) 48(1):80–90.

Chuang AY, Nielsen ME, Hernandez DJ, et al. The significance of positive surgical margin in areas of capsular incision in otherwise organ confined disease at radical prostatectomy. Journal of Urology (2007) 178(4 pt. 1):1306–1310.

Eastham JA, Kuroiwa K, Ohori M, et al. Prognostic significance of location of positive margins in radical prostatectomy specimens. Urology (2007) 70(5):965–969.

Evans AJ, Henry PC, Van der Kwast TH, et al. Interobserver variability between expert urologic pathologists for extraprostatic extension and surgical margin status in radical prostatectomy specimens. American Journal of Surgical Pathology (2008) 32(10):1503–1512.

Savdie R, Horvath LG, Benito RP, et al. High Gleason grade carcinoma at a positive surgical margin predicts biochemical failure after radical prostatectomy and may guide adjuvant radiotherapy. BJU Int. 2011 Oct 12. [Epub ahead of print]

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