Il carcinoma prostatico: selected topics di interesse anatomo-clinico

A. Galia

U.O.C. anatomia patologica

Cannizzaro

• Campionamento-processazione-taglio-colorazione

• Refertazione - istologia quantitativa - grading

• Protocolli di sorveglianza attiva (ruolo del

patologo)

• Zona anteriore

Come trattare le biopsie

other tumor types are not candidates for AS. Patients withvariants of acinar adenocarcinoma, including atrophic,pseudohyperplastic, and foamy gland variants, can becandidates for AS if the carcinoma is of appropriate Gleasongrade and extent in needle core tissue.

Perineural Invasion

The role of prostate needle biopsy PNI in treatmentplanning has been a source of considerable debate. WhetherPNI that is sufficiently extensive to be sampled on needlebiopsy signals an increased risk of extraprostatic extensionof cancer is controversial. Studies assessing the significanceof PNI have had varied results. Some studies have shownPNI on needle biopsy not to be predictive of extraprostaticextension, whereas others have shown that PNI significantlypredicts extraprostatic extension. In some studies, signifi-cance was found only on univariate analysis but not inmultivariate analysis.60,70,83–85

There is only one study, to our knowledge, dealing withthe significance of PNI on needle biopsy in patients who areotherwise candidates for AS.85 Cases with PNI hadsignificantly greater likelihood of having more than 2positive cores, compared with cases without PNI (56.9%versus 39.7%, respectively; P ¼ .02). Despite the greaterextent of cancer on biopsy, cases with and without PNI onbiopsy showed no significant difference in surgical margininvolvement (6% and 7.3%, respectively) or organ-confineddisease (84.3% and 91.6%, respectively). These resultssuggest that patients with PNI who otherwise meet criteriafor AS should not be excluded from that option.

Atypical Small Acinar Proliferation in Patients Eligible

for AS

Atypical small acinar proliferations or atypical foci aredefined as atypical glands with features suspicious forcarcinoma but that lack sufficient architectural or cytologicatypia for a definitive diagnosis of carcinoma.86–88 A lesion

labeled atypical could be a focus of cancer which, for variousreasons, cannot be identified as cancer; tangentially cutoutpouchings of high-grade prostatic intraepithelial neo-plasia; or a benign mimic of prostate cancer. In largerstudies,89 the incidence has been found to be 2.4% to 9%,with a median incidence of about 5%. The diagnosis ofatypical small acinar proliferations in prostate needle biopsycarries the risk of finding cancer in subsequent biopsy in40% to 50% of cases.90

Use of immunohistochemical stains can help resolve anatypical diagnosis in some cases. Absence of basal cellsconfirms the diagnosis of carcinoma in some cases that havesufficient atypical features. The 2 most commonly used basalcell markers are high–molecular-weight cytokeratins, de-tected by antibodies 34bE12 and p63, separately or as acocktail.91 Currently, a cocktail of antibodies reactive with a-methylacyl coenzyme-A racemase, high–molecular-weightcytokeratins, and/or p63 is commonly used.88,89

In cases with atypical glands in one or more cores withcancer detected in other cores, is it necessary to performimmunostains to investigate the atypical foci? Those atypicalfoci need to be investigated with immunostains only if theymean that a cancer diagnosis in the atypical foci wouldconvert treatment from AS to definitive radical treatment inthe short term. In general, if there is Gleason pattern 4 inone or more cores, no workup of atypical foci is necessary. Ifthere is a Gleason score 3 þ 3¼6 in less than one-third ofcores involving less than 50% of any single core and afinding of other foci of cancer that would significantlychange management, then the workup of atypical foci isnecessary.

Other Considerations

Many cancer attributes can predict aggressive clinicalphenotypes. Some of those situations are rare and, althoughnot formally evaluated, should likely exclude a patient from

Figure 1. Multiple cores embedded in aparaffin block often result in uneven levelsamong cores and result in the loss of tissuewhen cutting for histology.

1394 Arch Pathol Lab Med—Vol 138, October 2014 Active Surveillance in Prostate Cancer Patients—Amin et al

Come trattare le biopsie

Multiple biopsies per vial (and paraffin block) were used in approximately half of the centers that participated in

the survey, which is not recommended due to a presumption that tissue quality will be compromised.

The use of multiple biopsies per vial (and paraffin block) is supported by less extensive laboratory

loading and better facilities for immunohistochemistry

In terms of biopsy quality, it has been suggested that up to three cores could be safely embedded in one paraffin

block without compromising the biopsy quality

• Thechniques improvement

• Special embedding

• Consensus required

“No difference in the lengths of biopsies

regardless of whether they were processed individually or pooled”

P 63

Agobiopsia: cosa refertare

• Tipo istologico • Numero dei cilindri positivi • Sede dei cilindri positivi • Istologia quantitativa • Gleason grading • Altri reperti (solo se presenti) - invasione perineurale - estensione extraprostatica - ASAP - PIN

Agobiopsia: istologia quantitativa

• Numero dei cilindri positivi • Percentuale dei cilindri positivi • Percentuale lineare di carcinoma in ciascun cilindro • Percentuale lineare di carcinoma nel cilindro con il

maggiore ammontare di neoplasia (GPC) • Percentuale globale di carcinoma in tutti i cilindri (TPC) • Misura lineare (in millimetri) di carcinoma in ciascun

cilindro • Misura lineare (in millimetri) di carcinoma nel cilindro con il

maggiore ammontare di neoplasia • Misura lineare totale (in millimetri) della neoplasia in tutti i

cilindri

Problematiche relative alla istologia quantitativa

• Misura dei focolai discontinui di carcinoma

• Inadeguata lunghezza dei cilindri

• Frammentazione dei cilindri

• Sezioni inadeguate

• Se la lunghezza dei cilindri deve includere il tessuto extraprostatico

30-60%

Extent of cancer of less than 50% in any prostat needle biopsy core: how many millimeters

are there ? Montironi R et all. European Urology 2012

Extent of cancer of less than 50% in any prostat needle biopsy core: how many millimeters

are there ? Montironi R et all. European Urology 2012

Gleason grading

“Histologic grading is the clinically most useful tissue-

based predictor of prognosis for prostate cancer”

“Clinicians use various tools such Partin tables or Kattan normograms to predict outcomes. All of these tools

incorporate Gleason score”

Gleason grading

ISUP 2005 Original Gleason grading

score 6 score 7 score 8

SIGNIFICATO CLINICO DEL PATTERN 3

Neoplasia con score 6

• E’ relativamente indolente

• Non metastatizza ai linfonodi

(Am J Surg Pathol 2012)

• No “cancer specific deaths” dopo prostatectomia radicale

(BJU Int. July 2014)

• Non si deve fare diagnosi di Gleason score 2-4 su agobiopsia

• La quasi totalità dei pattern cribriformi devono essere refertati come Gleason pattern 4

• Nelle agobiopsie una componente di alto grado deve sempre essere inclusa nello score di Gleason (lo score

comprende “the most and the worst”)

• La presenza di singole cellule non rappresenta un Gleeason pattern 3

Perché non dare lo score 2-4 su agobiopsia

• Lo score 2-4 è estremamente raro su agobiopsia in paragone ai prelievi da TURP

• Scarsa riproducibilità tra gli esperti per i tumori di

basso grado • Scarsa correlazione con lo score su prostatectomia

• Può erroneamente indurre sia il medico sia il paziente

a considerare il tumore come indolente

ISUP 2005 modified Gleason system

Limita la definizione del pattern 3 ed amplia quella del pattern 4 ha determinato

tendenza all’ “upgrading”

miglioramento della concordanza del Gleason score tra agobiopsia e prostatectomia

Sorveglianza attiva criteri istopatologiche

• La valutazione dello score di Gleason è uno dei fattori più importanti per i pazienti in AS

• Una accurata distinzione del pattern 3 dal pattern 4 è elemento

critico per l’elegibilità ai protocolli di AS

• Solo ghiandole “poorly formed” (non attribuibili a tangenzialità)

e ghiandole cribriformi devono essere classificate come pattern

4

Sorveglianza attiva criteri istopatologici di esclusione

• Adenocarcinomi con prevalenti aspetti duttali • Carcinoma intraduttale non invasivo

• Carcinoma sarcomatoide o a piccole cellule

• Estensione extra prostatica

• Invasione linfo-vascolare

Zona anteriore della prostata

• Porzione della prostata localizzata anteriormente all’uretra costituita da

- tessuto periuretrale

- “corna” anteriori della zona posteriore

- zona di transizione

- stroma fibro-muscolare anteriore

• le prime tre zone possono contenere tessuto ghiandolare e carcinomi prostatici possono svilupparsi sia nella TZ sia nella AZ

Zona anteriore della prostata

• Meno visualizzata con metodiche di imaging

• Sede di neoplasie non palpabili

• Necessita di un maggior numero di biopsie

• E’ più accessibile con approccio transperineale

ISUP 2014

• Ghiandole cribriformi costituiscono pattern 4 • Ghiandole glomeruloidi costituiscono pattern 4 • Al carcinoma intraduttale senza componente invasiva

non si assegna il grading • Occasionali ghiandole poorly formed tra ghiandole ben

formate non costituiscono pattern 4 • In caso di morfologia borderline tra pattern 3 e

pattern 4, con artefatti da crush, occorre assegnare il grado 3

• Ghiandole ramificate costituiscono pattern 3 • Presenza di comedonecrosi anche focale costituisce

pattern 5

Reporting of Gleason score Prognostic Grade Groups

The overall Gleason score is based on the core with the highest Gleason score. Gleason score can be grouped and range from Prognostic Grade Group I (most

favorable) to Prognostic Grade Group V (least favorable)

• Gleason score 6 Prognostic Grade Group I

• Gleason score 3+4 Prognostic Grade Group II

• Gleason score 4+3 Prognostic Grade Group III

• Gleason score 8 Prognostic Grade Group IV

• Gleason score 9-10 Prognostic Grade Group V