Prostate Needle Biopsies: Impact of Aggregate Tissue Length

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Abstract: A study in our lab of 642 cases in 1993 and 21 cases in 1998 of prostate biopsy cases comparing the cancer diagnosis rate to aggregate biopsy tissue core lengths. An aggregate core length of >2.5 cm. was determined to be a generally significant breakpoint for an optimal cancer detection rate. Details of a proposed biopsy technique are presented, and some other interpretative parameters discussed. This has been published only on this website. In late 2016 & into 2017, I have been posting some "how to" videos on YouTube about agar pre-embedding and prostate biopsies (search YouTube with the term, "agar pre-embedding" (this page is posted there).

Key words: surgical pathology, histology, agar pre-embedding, prostate cancer, biopsy, biopsy operator technique.

Introduction:

The primary reason for performing patterned prostate biopsies is to discover adenocarcinoma at an early stage, other assessments being of ancillary value. It is possible to plan the biopsy technique so as to obtain an average length of 1.0 cm. of prostate tissue per biopsy core and to include the periprostatic (capsule) zone. What constitutes an adequate biopsy core and core series? We are not aware of any journal publication or instrument package insert detailing ultrasound-guided biopty-gun techniques for optimizing the biopsy sampling of the prostate relative to demonstrating the capsular zone. Adequacy pertains not only to sampling pattern, biopsy core lengths, and volume of biopsy cores...all relative to gland size, but also to whether the core contains prostate glandular tissue and the capsular interface. Stimulated by a series of patient samples with scanty cores, we considered the possibility that total aggregate biopsy length might be proportional to the rate of diagnostic yield.

Materials and Methods:

We evaluated a sequential total of 642 patients having office-based biopsies by twelve private-practice urologists in 1993, predominately under ultrasound guidance, with 1 to 9 biopsy cores per case. All biopsies were obtained using 18 gauge (1.2 mm width) "Biopty" types of spring-loaded guns with the needle core-sample notch being 17 mm in length. Cores were "blotted" from the needle notch with marked blot papers ^6,7 for a dual purpose:

1. to maintain intact tissue relationships if the cores were fragmented, and
   
2. to maintain tissue orientation so that the core ends might be kept in a labeled position as to biopsy needle-tip end (which should be the ventrad/anterior end) versus biopsy-gun end (which should be the dorsad/rectad/capsular end).
   

The cores were immediately fixed on the papers in this anatomical layout in 10% neutral buffered formalin, preventing core shrinkage and maintaining tissue relationships even when fragmented. The receiving pathologist or specially-trained pathologist assistant carefully removed the cores from the blot papers, arranged the cores relative to color-coded agar markers, with markers and three cores sequentially agar pre-embedded per paraffin block^6,7. Core measurements were taken at this point and recorded in the gross description in the pathology report. Step-cut sections from each block were mounted during microtome sectioning at 6 levels spaced entirely through each block (6 slides per block, 3 microtome ribbon frames per slide), with intervening paraffin ribbons saved for other studies, as necessary.^6,7

One of the twelve urologists was consistently perceived as obtaining the best (thickest, longest, almost always non-fragmented) biopsy cores. A thirteenth urologist, joining in 1996, was perceived as consistently producing the scantiest (thin, short, fragmented) biopsy cores. A comparative series of his first 21 patients in 1997 was evaluated. Results:

The 642 cases studied included 246 (38.3%)with cancer. A total of 3,006 biopsy cores, averaging 4.68 cores per patient, had an average core length of 1.09 cm. Aggregate per-case core lengths were arbitrarily divided into 3 ranges with the cancer detection rates noted (see Table 1, end of paper).

The urologist perceived as obtaining the best core biopsies had 47 of the 642 patients, 16 (34%) with cancer. Those 47 patients were sampled by a total of 135 cores having an average core length of 1.2 cm., averaging 2.87 cores per patient (see Table 2, end of paper). It is our impression that his cores seldom contained capsule.

In the separate 1997 cohort (below), the urologist perceived as obtaining the scantiest cores biopsied 21 patients, 10 (47.6%) with cancer. A total of 166 cores, averaging 7.9 cores per patient, had an average core length of 0.9 cm. (see Table 3, end of paper). His bilateral transition-zone cores, obtained on 20 cases, averaged 1.36 cm. each so that remaining peripheral cores averaged only 0.79 cm. each. These peripheral, non-transitional zone biopsy sets often contained cores devoid of microscopic prostatic glands, the tissue containing only loose periprostatic soft tissue, being an indication that the gland itself was not penetrated and sampled. Such aglandular cores were obtained at an average of 2 cores per case, a spaced periphery sampling averaging only 4 true gland cores. In effect, the goal of an octant sampling became, at best, a modified sextant sampling. Transitional zone biopsies, in order to reach that deeper, more anterior gland zone, are obtained by a technique similar to that of the “best cores” urologist (described below) but with the needle tip advanced even deeper in the gland prior to triggering.

Discussion:

It appears to be widely accepted that greater numbers of systematically spaced core biopsies produce an enhanced cancer detection rate^2,8, and pathologists are increasingly aware of the importance of histologic processing techniques in both the actual discovery of any cancer contained in prostate biopsies and in maximally portraying related information for clinical decision making. Basics of surgical pathology sampling techniques tell us that a systematically spaced sextant or octant set of full-length biopsies would sample more prostate tissue and have a more optimal rate of detection of prostate cancer than shorter or fewer biopsy samplings (an optimal set of six cores samples 0.2%...HERE...of a 30 gram prostate). Stamey, the original champion of systematically patterned core biopsies, has recently stated that an adequate sextant sample is no less than 5cm. of aggregate core length⁸.

Intense processing: We have been involved in the evaluation of patients for prostate cancer with biopty-gun techniques since 1990, now averaging at least 800 biopsy sets per year. We concieved an intense process nearly from the beginning. In our...about 1992...comprehensive study of 540 cases (105 cancerous), the processing routine necessary to insure 100% detection of every cancer within the submitted sample of cores was found to be five step-cut levels averaging 18 frames of section entirely through each block (we recommended a safety margin of 6 levels)^6,7. Our step-cut process saves ribbon (6 slides per block, 3 microtome ribbon frames per slide), with intervening paraffin ribbons saved (for additional H&Es or other special studies) at least until the case is signed out. Allsbrook's subsequent paper contains a graphic which excellently illustrates the step-cut process, the report suggesting that 3 levels could be adequate⁴. Epstein later indicates that less than 3 levels misses important findings¹. Sextant cores, at best, represent a sample analysis of less than 0.2 % of a 30 gram prostate gland. So, we continue to prefer and to strongly recommend step-cutting as above in an effort to eliminate the hazard of a false negative surgical pathology determination on cores which often contain a minute representation of a sizeable (11 of 29 single-microfocus cases were radicals and had tumors greater than 9 mm., 3 of the 11 having positive surgical margins) cancer^6,7. In the interval to date, we have not become aware of any “missed” cases. It is a simpler and more expeditious process to maintain a system of step-cutting all blocks rather than to cut some slides and later recut for various purposes as Humphrey proposes⁵.

Since prostate cancer has a strong tendency for peripheral location in the gland, we desired to determine whether the cancer diagnosis rate would nevertheless be highest in cases with longer aggregate lengths. We discovered that, whether on the global average or by the urologist producing the best or scantiest biopsies, the cancer detection rate was consistently and significantly higher in the patients having an aggregate biopsy set core length >2.6 cm. Recognizing this critical detection break-point, we conclude that a longer aggregate length is better.

Further stratification of cases was not done as it was not feasible to retrospectively retrieve clinical information (PSA level, presence of a nodule, strength of indications for biopsy, etc.) from private practice offices in a large case series. Such factors are, however, highly relevant to the cancer detection rate.

Miscellaneous observations included:

1. the rarity of octant sampling in 1993,
   
2. an estimate of less than 5% of cores being aglandular (not from the actual prostate gland),
   
3. presence of rectal mucosa attached with about 25% of cores,
   
4. macroscopically visible, thin, stringy, periprostatic "tails" on one end of 15% of cores,
   
5. and the presence of the histo-morphological capsule boundary on the opposite tissue-core end from that expected within the block according to the technical orientation method.
   

Biopsy misdirection and/or instrument recoil are the likely cause of aglandular core samples. We suspect that rectal mucosa is obtained when gun triggering occurs too superficially, prior to sufficient advancement of the biopsy needle tip. Discordant block orientation-system location of the capsule is possible when cores are hurriedly blotted end-over-end from the needle in a wiping motion rather than softly blotted upward from the needle in a touch-prep-like motion. Loose fibrofatty areolar, extracapsular tissue corresponds to the above-noted “tail”. We estimate that the capsule was visible in 25% of cases; and we strongly recommend that any designation of a core end as the capsular end be a histomorphological determination, not a block orientation-only designation.

The "best cores" urologist indicated that his technique carefully correlates the biopsy effort with the real-time ultrasound image, pushing the needle tip snugly but not deeply into the prostate gland, bracing the gun arm firmly, then triggering the device. Theoretically, this needle-tip positioning causes the core sample to be taken deep to, not including, the prostatic capsule.

Biopty Gun Firing: Deriving from the above observations, we propose a suggestion for the biopsy-operator that optimal cores (intact, good length, capsule included) might be obtained with the biopty gun: (1) using careful ultrasound guidance, (2) placing the needle through the rectal wall, (3) barely advancing the needle tip to the surface of the prostate gland, (4) and nullifying any recoil-caused misdirection by exerting strong effort to brace the gun. Such cores might encourage pathologists to diligently go beyond a mere diagnosis of the presence or absence of cancer. Longer cores portraying more cancer additionally allow a better appreciation of the Gleason pattern (especially to avoid undergrading)^1,3, a better chance at detecting perineural space invasion, and a better chance at estimating quantity and distribution of cancer for staging⁸. Cores which clearly contain capsular boundary further allow some commentary as to the relationship of tumor to this boundary.

Bibliography:

1. Brat JB, Wills ML, Lecksell KL, Epstein JI. How Often Are Diagnostic Features Missed with Less Extensive Histologic Sampling of Prostate Needle Biopsy Specimens? Am J Surg Pathol 1999; 23:257-262.
   
2. Hodge KK, McNeal JE, Terris MK, Stamey TA. Random Systematic Versus Direct Ultrasound Guided Transrectal Core Biopsies Of The Prostate. J Urol 1989; 142:71-74.
   
3. Iczkowski KA, Bostwick DG, The Pathologist as Optimist...Cancer grade Deflation in Prostate Needle Biopsies. Am J Surg Pathol 1998; 22:1169-1170.
   
4. Lane R, Lane C, Mangold K, Johnson M, Allsbrook W. Needle Biopsies of the Prostate: What Constitutes Adequate Histologic Sampling? Arch Pathol Lab Med 1998; 122:833-835.
   
5. Reyes A, Humphrey P. Diagnostic Effect of Complete Histologic Sampling of Prostate Needle Biopsy Specimens. Am J Clin Pathol 1998; 109:416-422.
   
6. Shaw E, Daniel B, Wofford E, Carter J, Processing Prostate Needle Biopsy Specimens for 100% Detection of Carcinoma. Am J Clin Pathol 1995; 103:507.
   
7. Shaw E, Daniel B, Wofford E, Carter J, Prostate Biopsies: Optimized Cancer Detection and Staging. J SC Med Assoc 1996;92:261-266.
   
8. Stamey TA. Making The Most Out Of Six Systematic Sextant Biopsies. Urology 1995; 45:2-12.
   
9. Stamey TA, McNeal JE, Yemoto CM, Sigal BM, Johnstone IM. Biological Determinants of Cancer Progression in Men With Prostate Cancer. JAMA 1999; 281:1395-1400.
   

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     (posted 6 Sept.1999; adjusted 6 February 2017)