Portal de Periódicos da CAPES

Updated Protocol for the Examination of Specimens From Patients With Carcinomas of the Prostate Gland

2006; American Medical Association; Volume: 130; Issue: 7 Linguagem: Inglês

10.5858/2006-130-936-upfteo

1543-2165

John R. Srigley, Mahul B. Amin, Jonathan I. Epstein, David J. Grignon, Peter A. Humphrey, Andrew A. Renshaw, Thomas M. Wheeler,

Colorectal Cancer Screening and Detection

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical resection specimens and selected biopsies in patients with cancer. The College regards certain reporting elements in the "Surgical Pathology Cancer Case Summary (Checklist)" portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice.The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the essential checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with the document. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of this document.This protocol applies to invasive carcinomas of the prostate gland only. The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) TNM classification system for the staging of prostate gland tumors is recommended.This protocol applies only to carcinomas of the prostate gland. The histologic classification of prostate carcinoma is recommended and shown in the following.1 However, this protocol does not preclude the use of other systems of classification or histologic types. Mixtures of different histologic types should be indicated.The Gleason grading system is recommended for use in all prostatic specimens containing adenocarcinoma, with the exception of those showing treatment effects, usually in the setting of androgen withdrawal.2–5 Gleason score is an important parameter used in nomograms, such as the Partin tables, which guide individual treatment decisions.6 Readers are referred to the recommendations of a recent consensus conference dealing with the contemporary usage of the Gleason system.7 The Gleason score is the sum of the primary (most predominant in terms of surface area of involvement) 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 addition to the Gleason score, for example, Gleason score 7 (3,4) or 7 (3+4).In needle biopsy specimens, it is recommended that Gleason scores be assigned for each specimen (container). In addition, a global or composite score reflecting all specimens may be provided.In needle biopsy specimens in which there is a minor secondary component (<5% of tumor) and in which the secondary component is of higher grade, the latter should be reported. For instance, a case showing more than 95% Gleason 3 and less than 5% Gleason 4 should be reported as Gleason score 7 (3,4 or 3+4). Conversely, if a minor secondary pattern is of lower grade, it need not be reported. For instance, when there is more than 95% Gleason score 4 and less than 5% Gleason 3, the score should be reported as Gleason 8 (4,4).In needle biopsy specimens in which more than 2 patterns are present, and the worst grade is neither the predominant nor the secondary grade, the predominant and highest grade should be chosen to arrive at a score (eg, 75% grade 3, 20%–25% grade 4, <5% grade 5) is scored as 3 + 5 = 8.Rules of grading similar to the previous apply to transurethral resection and enucleation specimens.Tertiary Gleason patterns are common in radical prostatectomy specimens. When Gleason pattern 5 is present as a tertiary pattern, its presence should be recognized in the report. For instance, in a situation in which the primary Gleason grade is 3, the secondary is 4, and there is less than 5% Gleason 5, the report should indicate a Gleason score of 7 (3,4) with tertiary Gleason pattern 5.In most radical prostatectomy specimens, a dominant nodule is not present, and the Gleason score is based on the tumor present in the entire gland. When more than 1 separate tumor is clearly identified, the Gleason scores of individual tumors can be recorded separately, or, at the very least, a Gleason score of the dominant or most significant lesion should be recorded. For instance, if there is a large Gleason score 4 (2,2) transition zone tumor and a separate smaller Gleason score 8 (4,4) peripheral zone cancer, both scores should be reported, or, at the very least, the latter score should be reported rather than these scores being averaged.There are many methods of estimating the amount of tumor in prostatic specimens.8–17 In core biopsies, the absolute number or percentage of cores involved, the linear extent of involvement in millimeters, and the proportion (percent) of surface area of prostatic tissue involved may be used. In transurethral resections, the proportion (percent) of tissue involved by carcinoma, the number of positive chips, and the ratio or percentage positive chips to total chips may be used. In subtotal and radical prostatectomy specimens, the percentage of tissue involved by tumor can also be "eyeballed." Additionally, in these latter specimens, it may be possible to measure a dominant tumor nodule in at least 2 dimensions and/or to indicate the number of blocks involved by tumor over the total number of prostatic blocks submitted.For the purpose of this protocol, it is suggested that, at the very least, the estimated proportion (percent) of prostatic tissue involved by tumor be included for all specimens.Occasionally in needle biopsies, periprostatic fat is present and involved by tumor.89 This observation should be noted because it indicates that the tumor is at least pT3a in the TNM system. Furthermore, if seminal vesicle tissue is present (either unintentionally or intentionally, as in a directed biopsy) and involved by tumor, this should be reported because it indicates that the tumor is at least pT3b. Seminal vesicle invasion is defined by involvement of the muscular wall.8918 At times, especially in needle biopsy specimens, it is difficult to distinguish between seminal vesicle and ejaculatory duct tissue. It is important not to overinterpret ejaculatory duct as seminal vesicle because involvement of the former by tumor does not constitute pT3b disease. If there is doubt as to whether the involved tissue represents seminal vesicle or ejaculatory duct, then invasion of seminal vesicle should not be definitively diagnosed.Perineural invasion in core needle biopsies has been associated with EPE in some correlative radical prostatectomy studies, although its exact prognostic significance remains to be determined.919–22 Perineural invasion has also been found to be an independent risk factor for predicting an adverse outcome in patients treated with external beam radiation. The value of perineural invasion as an independent prognostic factor, however, has been questioned in a multivariate analysis.22The diagnostic term PIN, unless qualified, refers to high-grade PIN.23 Generally, low-grade PIN is not reported. The presence of isolated PIN should be reported in all biopsy specimens.9 The reporting of PIN in biopsies with carcinoma is considered optional but may be important, especially in the context of limited (minimal) adenocarcinoma. High-grade PIN in a biopsy without evidence of carcinoma is a risk factor for the presence of carcinoma on subsequent biopsies.2425 The reporting of high-grade PIN in prostatectomy specimens is optional.Specimens weighing 12 g or less should be submitted in their entirety, usually in 6 to 8 cassettes.2627 For specimens greater than 12 g, the initial 12 g are submitted (6–8 cassettes), and 1 cassette for every additional 5 g may be submitted.In general, random chips are submitted; however, if some chips are firmer or have a yellow or orange-yellow appearance, they should be preferentially submitted.If an unsuspected carcinoma is found in tissue submitted, and it involves 5% or less of the tissue examined, the remaining tissue may be submitted for microscopic examination, especially in younger patients.A radical prostatectomy specimen may be submitted in its entirety or partially sampled in a systematic fashion.2829 For partial sampling in the setting of a grossly visible tumor, the tumor and associated periprostatic tissue and margins, along with the entire apical and bladder neck margins and the junction of each seminal vesicle with prostate proper, should be submitted. If there is no grossly visible tumor, a number of systematic sampling strategies may be used. One that yields excellent prognostic information involves submitting the posterior aspect of each transverse slice along with a mid anterior block from each side. The anterior sampling detects the T1c cases arising in the transition zone and extending anteriorly.29 The entire apical and bladder neck margins and junction of each seminal vesicle with prostate should also be submitted.The entire surface of the prostate should be inked to evaluate the surgical margins.28–36 Usually, surgical margins should be designated as "negative" if tumor is not present at the inked margin and as "positive" if tumor cells touch the ink at the margin. When tumor is located very close to an inked surface but is not actually in contact with the ink, the margin is considered negative. Positive surgical margins should not be interpreted as EPE. Intraprostatic margins are positive in the setting of capsular incision (so-called pT2+ disease).28 If the surgical margin is positive, the pathologist should state this explicitly, although this finding is not relied on for pathologic staging. The specific locations of the positive margins are useful to report, and there should be some indication of the extent of margin positivity (eg, unifocal versus multifocal, number of positive sites [blocks], linear extent in millimeters).Extraprostatic extension is the preferred term for the presence of tumor beyond the confines of the prostate gland.283031 Tumor abutting on or admixed with fat constitutes EPE. Tumor involving loose connective tissue in the plane of fat or beyond, even in the absence of direct contact between tumor and adipocytes, indicates EPE. Extraprostatic extension also may be reported when tumor involves perineural spaces in the neurovascular bundles, even in the absence of periprostatic fat involvement. In certain locations, such as the anterior prostate and bladder neck regions, there is a paucity of fat, and in these locations EPE is determined when the tumor extends beyond the confines of the normal glandular prostate. Sometimes there is a distinct bulging tumor nodule, which may be associated with a desmoplastic stromal reaction. The specific location(s) and the number of sites (blocks) of EPE are useful to report. Descriptors of EPE (focal, nonfocal) may be used. The definition of focal versus nonfocal is subjective, but focal EPE equates with only a few neoplastic glands outside the prostate, and nonfocal EPE is more extensive spread beyond the prostatic edge. Focal or nonfocal EPE may involve 1 or more sites.The apex should be carefully examined because it is a common site of margin positivity.28–31 At the apex, tumor admixed with skeletal muscle elements does not constitute EPE. The apical and bladder neck surgical margins should be submitted entirely, preferably with a perpendicular sectioning technique. Microscopic involvement of bladder neck muscle fibers in radical prostatectomy specimens should not be equated with a pT4 designation. The latter requires gross involvement of the bladder neck, generally with margin positivity. A recent study has shown that patients with microscopic bladder neck involvement have recurrence rates similar to patients with seminal vesicle involvement (pT3b).37The protocol recommends the use of the TNM staging system for carcinoma of the prostate of the AJCC and the UICC, as shown in the following.3839By AJCC/UICC convention, the designation "T" refers to a primary tumor that has not been previously treated. The symbol "p" refers to the pathologic classification of the TNM, as opposed to the clinical classification, and is based on gross and microscopic examination. pT entails a resection of the primary tumor or biopsy adequate to evaluate the highest pT category, pN entails removal of nodes adequate to validate lymph node metastasis, and pM implies microscopic examination of distant lesions. Clinical classification (cTNM) is usually carried out by the referring physician before treatment during initial evaluation of the patient or when pathologic classification is not possible.Pathologic staging is usually performed after surgical resection of the primary tumor. Pathologic staging depends on pathologic documentation of the anatomic extent of disease, whether or not the primary tumor has been completely removed. If a biopsied tumor is not resected for any reason (eg, when technically unfeasible), and if the highest T and N categories or the M1 category of the tumor can be confirmed microscopically, the criteria for pathologic classification and staging have been satisfied without total removal of the primary cancer.For identification of special cases of TNM or pTNM classifications, the "m" suffix and "y," "r," and "a" prefixes are used. Although they do not affect the stage grouping, they indicate cases needing separate analysis.The "m" suffix indicates the presence of multiple primary tumors in a single site and is recorded in parentheses: pT(m)NM.The "y" prefix indicates those cases in which classification is performed during or following initial multimodality therapy (ie, neoadjuvant chemotherapy, radiation therapy, or both chemotherapy and radiation therapy). The cTNM or pTNM category is identified by a "y" prefix. The ycTNM or ypTNM categorizes the extent of tumor actually present at the time of that examination. The "y" categorization is not an estimate of tumor prior to multimodality therapy (ie, before initiation of neoadjuvant therapy).The "r" prefix indicates a recurrent tumor when staged after a documented disease-free interval, and is identified by the "r" prefix: rTNM.The "a" prefix designates the stage determined at autopsy: aTNM.Tumor remaining in a patient after therapy with curative intent (eg, surgical resection for cure) is categorized by a system known as R classification, shown in the following.For the surgeon, the R classification may be useful to indicate the known or assumed status of the completeness of a surgical excision. For the pathologist, the R classification is relevant to the status of the margins of a surgical resection specimen. That is, tumor involving the resection margin on pathologic examination may be assumed to correspond to residual tumor in the patient and may be classified as macroscopic or microscopic according to the findings at the specimen margin(s).By AJCC/UICC convention, vessel invasion (lymphatic or venous) does not affect the T category indicating local extent of tumor unless specifically included in the definition of a T category. In all other cases, lymphatic and venous invasion by tumor are coded separately as follows.Lymphatic Vessel Invasion (L)Venous (Large Vessel) Invasion (V)Isolated tumor cells (ITCs) are single cells or small clusters of cells not more than 0.2 mm in greatest dimension. Lymph nodes or distant sites with ITCs found by either histologic examination, immunohistochemistry, or nonmorphologic techniques (eg, flow cytometry, DNA analysis, polymerase chain reaction amplification of a specific tumor marker) should be classified as N0 or M0, respectively. Specific denotation of the assigned N category is suggested as follows for cases in which ITCs are the only evidence of possible metastatic disease.4041 The assessment of ITCs in the context of prostatic adenocarcinoma is considered investigational and their biologic significance is unknown.