Surgical Oncology (2009) 18, 200e202

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REVIEW

Perineural and lymphovascular invasion on prostaticbiopsy: Pathological assessment and significance

Alex Freeman

University College Hospital NHS Trust, London, UK

KEYWORDSPerineural;Lymphovascular;Prostate cancer;Biopsy

E-mail address: alex.freeman@ucl

0960-7404/$ - see front matter ª 200doi:10.1016/j.suronc.2009.02.010

Abstract

The importance of Gleason grade on prostatic needle biopsy specimens is widely accepted asa significant histopathological prognostic factor in the assessment of prostatic carcinoma.However, the value of other pathological variables used in the reporting of prostatic needlebiopsies such as perineural or lymphovascular invasion is more controversial. This reviewexamines the evidence for the utility of these pathological factors as prognostic indicatorsfor prostatic carcinoma and the limitations in their assessment on needle biopsies.ª 2009 Elsevier Ltd. All rights reserved.

Contents

Perineural invasion (PNI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200Lymphovascular invasion (LVI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202

Perineural invasion (PNI)

PNI is defined as the presence of prostatic carcinomatracking along or around a nerve [1]. The assessment ofthis factor relies on a number of variables that mayreflect local practice of the surgeon, pathologist orpathology laboratory including the number of cores takenand biopsy protocol, number of levels examined perbiopsy, number of pathologists reporting, presence of

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9 Elsevier Ltd. All rights reserved

nerves within the biopsy. Furthermore the reporting ofPNI by pathologists is not mandatory and may frequentlybe omitted. All of these elements combine to account forthe wide variation in the incidence of PNI reportedbetween laboratories.

Although PNI is a known risk factor for malignancies atother sites [2], there are conflicting reports about its signifi-cance in prostatic carcinoma. It is postulated as a potentialmechanism for spread of tumour beyond the prostate

.

Table 1. Correlation of PNI on prostatic biopsy with EPEin subsequent radical prostatectomy.

Author % EPE Significant in multivariate analysis

Vargas [5] 38 YesEgan [6] 49 NoTaille [7] 52 YesUkimura [8] 61 Yes

PNI , perineural invasion; EPE, extraprostatic extension.

Perineural and lymphovascular invasion 201

(extraprostatic extension) by the migration of tumour cellsalong the nerve bundles [3]. However, even though thisappears as a credible hypothesis, up to 57% of surgeons statethat the reporting of PNI in a pathology report would notinfluence their management of a patient [4].

Several studies have examined the relationship betweenPNI in prostatic needle biopsies and presence of extrapro-static extension (EPE) of prostatic carcinoma on subsequentradical prostatectomy [5e8]. The majority of these studiesreport that PNI is an independent significant prognosticfactor, correlating with the presence of EPE in the resectionspecimen (Table 1).

Further studies have correlated the presence of PNI withEPE and risk of clinical or biochemical recurrence, usingvariable values for PSA from >0.1 to >0.4 ng/ml as indic-ative of biochemical relapse. Although two of these studiesfound no significance between PNI and clinical orbiochemical recurrence [9,10], others found that PNI wasan independent prognostic factor for prostatic carcinomarecurrence on univariate or multivariate analysis ([11e14];see Table 2).

Thus, even accounting for the possible under-reportingof PNI in prostate needle biopsies as a result of variability inbiopsy protocol, examination of levels per biopsy specimen,interpretation and reporting between pathologists andabsence of nerves in some specimens (giving an uninfor-mative sample but often recorded as negative for PNI), theweight of evidence appears to suggest that PNI is an inde-pendent prognostic factor for EPE and subsequent localrecurrence in prostatic carcinoma.

In fact, excising the neurovascular bundle in patientwith PNI at needle biopsy has been shown to result ina reduction in the incidence of positive margins at radicalprostatectomy in 17% cases and a decrease in the extent ofpositive margins in 11% cases [15].

Table 2 Studies examining correlation of PNI with biochemical

Author No. patientswith PNI (%)

PSA recurrence, n

Ravery [9] 28 (43) >0.1Freedland [10] 33 (17) >0.2De La Taille [11] 77 (24) 0.2 or greaterD’Amico [12] 53 (7) >0.1Quinn [13] 65 (10) >0.4Sebo [14] 103 (23) 0.4 or greater

ND Z not done.

An excellent systematic review on the subject ofPNI written in 2006 elegantly reports the variability ofinformation provided in published papers examining thesignificance of PNI in prostatic biopsies and the inherentproblems with interpreting their findings [16].

Lymphovascular invasion (LVI)

There is little information about the significance of lym-phovascular invasion in prostate needle biopsies. Thereasons for this may include the relative rarity of thisfinding on biopsy and the fact that pathologists frequentlyare not recording this information in their report.Furthermore, interpretation is limited by the difficulty indistinction of true lymphovascular invasion from retractionartefact (where a group of tumour cells appears to besurrounded by a clear space mimicking a vascular channel)that is artificially produced by the processing of the biopsy.Immunocytochemistry may also be uninformative as thefocus of suspicion frequently is not present on deeper levelsexamined.

A study in 2005 examined the significance of lympho-vascular invasion in 504 patients after radical prostatec-tomy [17]. Their findings showed that LVI was seen in 106cases (21%). A correlation was seen between LVI andpreoperative PSA, tumour stage, Gleason score, positivemargins, EPE, seminal vesicle invasion and PNI. In multi-variate assessment after controlling for Gleason grade,stage and margins, LVI was also found to be an independentpredictor of PSA recurrence and cancer specific survival.Similar results are also reported in more recent studies[18,19].

Summary

The assessment of PNI and LVI in prostatic needle biopsiesand their significance in predicting prostate cancer recur-rence remains a subject of debate. This may result partiallyfrom the variability in the assessment and reporting ofthese factors in the published literature. Recent publica-tions show that the majority of studies examining PNIsuggest that it correlates with risk of EPE and representsa significant prognostic factor in predicting prostate cancerrecurrence. However, the evidence for LVI as a significantfactor in predicting recurrence of survival relies on infor-mation from radical prostatectomy series and thus its value

PSA recurrence post radical prostatectomy.

g/ml Significance on univariate/multivariate analysis

No/NDNo/NoND/Yes (p Z 0.12)ND/Yes (for low risk patient)Yes/Yes (p Z 0.005)Yes/Yes (p Z 0.008)

202 A. Freeman

in prostatic needle biopsies independent of Gleason gradeor other pathological variables remains uncertain.

References

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