Prostate carcinoma I: prognostic factors in radical prostatectomy specimens and pelvic lymph nodes

Mini rev Article PROGNOSTIC FACTORS IN RADICAL PROSTATECTOMY MONTIRONI et al.

Prostate carcinoma I: prognostic factors in radical prostatectomy specimens and pelvic lymph nodes RODOLFO MONTIRONI, ROBERTA MAZZUCCHELLI, MARINA SCARPELLI, ANTONIO LOPEZ-BELTRAN* and GREGOR MIKUZ† Institute of Pathological Anatomy and Histopathology, Polytechnic University of the Marche Region, Ancona, Italy, *Department of Pathology, Reina Sofia University Hospital and Cordoba University Medical School, Cordoba, Spain, and †Department of Pathology, University of Innsbruck School of Medicine, Innsbruck, Austria Accepted for publication 26 September 2005

KEYWORDS

HISTOLOGICAL GRADE OF CANCER

prostate cancer, radical prostatectomy, prognostic factor, Gleason score, perineural invasion, tumour volume, pelvic lymph nodes

The Gleason score assigned to the tumour at RP is the most powerful predictor of progression after RP [11–18]. A recent Conference on Gleason Grading of Prostatic Carcinoma was organized by the International Society of Urological Pathology [11]. A consensus was reached on several specific issues related to applying the Gleason system. The Gleason score is the sum of the primary (most predominant) Gleason grade and the secondary (second most predominant) Gleason grade. Where no secondary Gleason grade exists, the primary Gleason grade is doubled to arrive at a Gleason score. The primary and secondary grades should be reported in parenthesis after the Gleason score, i.e. Gleason score 7 (3 + 4). Although Gleason scores range from 2 to 10, the grade seen at RP tends to be more restricted. The Gleason score is emphasized as the grading system of choice and using the terms ‘well’, ‘moderately’ and ‘poorly’ differentiated for grading is not recommended [4]. When patients are under androgen blockade before surgery, the Gleason system cannot be applied [18].

INTRODUCTION The increase in the rate of prostate cancer detection has induced a sharp increase in the number of radical prostatectomies (RPs) [1–6]. The proper examination of RP specimens by the pathologists is critical in accurately determining the prediction of patient outcome. The pathology report should include relevant clinical information (Table 1) [7] as well as provide prognostically useful data derived from the evaluation of the RP specimen (Table 2) [4,7–9] (see [4] also for the classification of the prognostic factors according the College of American Pathologists). In this article, we review the pathology reporting of RP specimens and pelvic lymph nodes.

PATHOLOGY REPORTING OF RP SPECIMENS HISTOLOGICAL TYPE OF CANCER The histological classification of prostate carcinoma is shown in Table 3 [10]. In general, >95% of cases of prostatic carcinoma are acinar adenocarcinoma (Fig. 1A). In recent years, several new and unusual histological variants or subtypes have been identified. The biological behaviour of many of these variants may differ from acinar adenocarcinoma and proper clinical management depends on an accurate diagnosis. It is recommended that subtypes, such as small cell, ductal and mucinous, should be reported if they are noted histologically (Fig. 1B). Mixtures of different histological types should also be indicated [10].

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As to grading variations of acinar adenocarcinoma of the prostate the tumour should be graded solely based on the underlying architecture. When dealing with variants of adenocarcinoma such as ductal adenocarcinoma, this tumour should be graded as Gleason score 4 + 4 = 8, while retaining the diagnostic term of ductal adenocarcinoma to denote their unique clinical and pathological findings. There is no consensus on the way mucinous (colloid) carcinoma should be scored. Some authors think that all mucinous carcinomas should be assigned a Gleason score of 8, while others suggest that the extracellular mucin should be ignored and the tumour graded based on the underlying architectural pattern. Small cell carcinoma

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should not be assigned a Gleason grade. The appropriateness of assigning a Gleason score to sarcomatoid carcinoma is uncertain. In general, a Gleason grade of 5 is assigned to the sarcomatoid component, whereas the glandular component is graded in the usual fashion. A certain proportion of RP specimens are found to contain more than two grades (i.e. tertiary Gleason pattern). Tumours which are Gleason score 4 + 3 = 7 with a tertiary pattern 5, while behaving worse than Gleason score 4 + 3 = 7 tumours with no tertiary pattern 5, have a much lower incidence of seminal vesicle invasion (SVI) and lymph-node metastases than tumours which are Gleason score 4 + 5 = 9 [19]. Consequently, in RP specimens it would be misleading to derive the Gleason score by adding the most common Gleason pattern and the highest Gleason pattern. It was the consensus of the International Society of Urological Pathology that for a RP specimen the Gleason score is assigned based on the primary and secondary patterns, with a comment as to the tertiary pattern [11]. There is no consensus on reporting secondary patterns of higher grade when present to a limited extent. In RP specimens with a tumour nodule having 98% Gleason pattern 3 and 2% pattern 4, some uropathologists would diagnose these foci analogously to that done on needle biopsy and interpret the case as Gleason score 3 + 4 = 7, regardless of the percentage of pattern 4. Others would note these tumours as Gleason score 3 + 3 = 6 with a minor component of Gleason pattern 4. The rationale for the latter method is based on RP data; cancers with >95% Gleason pattern 3 and 5% of the tumour [11]. In the setting of high-grade cancer lower grade 485

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patterns should be ignored if they occupy 70% or