Context.—

Core biopsies are standard of care for diagnosis and surveillance of prostate cancer. Fragmentation makes numeric assessment of cancer challenging and increases risk of inaccurate staging, with direct implications on management.

Objective.—

To determine factors responsible for fragmentation at our institution.

Design.—

Prostate core biopsies performed at 2 hospital sites during 1 week were prospectively identified. Biopsies were received in multipart formalin jars, either mounted on a nonadherent dressing pad (Telfa, Medtronic Inc) or freely suspended, and grossed by experienced pathologists’ assistants. Fragmentation was defined as the difference between the number of cores sent by the clinician and the number of cores counted by the pathologist on microscopy.

Results.—

Forty-six cases (15 benign; 31 malignant) with 535 specimen jars were identified, of which 309 of 535 (57.8%) had >1 biopsy core per jar; 230 of 535 (43%) were received mounted on Telfa and 185 of 535 (34.6%) had histologic evidence of adenocarcinoma. Overall fragmentation rate was 157 of 535 (29.3%). Lowest fragmentation rate was seen when 1 core was submitted per jar regardless of mounting method (31 of 226; 14% for single versus 126 of 309; 41% for >1 per jar; P < .001). For 1 Telfa-mounted core, rate of fragmentation was 5 of 18 (27.8%) versus 26 of 203 (12.8%) when unmounted (P = .24). Significant increase in fragmentation of Telfa-mounted cores was seen when there were 3 per jar (32 of 70; 46% mounted fragmented versus 9 of 47; 19% unmounted fragmented specimens; P = .01).

Conclusions.—

Submission of >1 biopsy core per jar and use of Telfa for mounting are associated with increased fragmentation. We recommend limiting submission to 1 core per jar and avoid mounting cores on Telfa pads.

Prostate core biopsies (PCBs) are the standard of care for the diagnosis of prostate cancer. The volume of cancer on core biopsy is a powerful predictor of the pathologic stage at radical prostatectomy and the outcome after treatment and serves as an important tool for risk stratification and selection of patients for active surveillance of their cancer.1–3  The protocol for reporting cancer in a PCB as set forth by the College of American Pathologists recommends including the number of positive cores and the highest percentage of core involvement by prostate cancer as part of tumor quantitation metrics in the final pathology report.4  Fragmentation of PCBs makes this numeric assessment challenging. There is also a significant risk of understaging or overstaging cancer, which can have implications on patient management.5 

Factors including the number of prostate cores submitted per specimen jar, the presence of cancer in the biopsy core, and its Gleason score have been previously shown to influence the integrity of PCBs.5,6  At our institution, PCBs from one of our hospital locations have been historically mounted on an absorbent nonadherent dressing pad (Telfa, Medtronic Inc) at the time of specimen collection in the operating room. In this study, we sought to determine if the method of submission of a PCB, specifically, the mounting of biopsy cores on Telfa and number of cores submitted per jar, were associated with increased fragmentation.

Core biopsies from the prostate performed during 1 week were prospectively identified. These included biopsies performed at 2 main locations (location 1: Center of Advanced Medicine/Barnes Jewish Hospital, St Louis, Missouri; location 2: Barnes West County Hospital, St Louis, Missouri). All clinicians involved in the study were experienced urologists performing high volumes of PCB procedures. Individual specimens were received separately and processed using identical methods in the same laboratory by qualified pathologists’ assistants.

Data were collected from the final pathology reports and included the number of prostate cores counted by the grosser per specimen jar, the use of Telfa dressing pad for specimen mounting at the time of collection of the biopsy in the operating room, the type of tissue fixative used, and the final diagnosis. The highest Gleason score and the prognostic grade group were also recorded when adenocarcinoma of the prostate was present. Clinical procedure notes were reviewed from the electronic medical records for information regarding the reason for biopsy, the number of prostate cores obtained, the gauge of the biopsy needle used for specimen retrieval, the biopsy approach (transperineal versus transrectal), and the healthcare provider performing the biopsy. PCB fragmentation was defined as the difference in the number of prostate cores recorded in the operative procedure note by the clinician and the number of cores counted by the pathologist on microscopic examination. When this information was unavailable in the procedure note, the number of cores counted by the grosser was used for calculation and determination of core fragmentation. The study was exempt from review by the Institutional Review Board of Washington University School of Medicine (ID 202307137).

Statistical analysis was performed using IBM SPSS statistics package for Windows, version 27 (IBM Corp, Armonk, New York). Statistical significance was determined using a χ2 test for categorical data and an independent-sample t test for parametric data. For nonparametric data, proportions were calculated, and a χ2 test was applied for significance. For parametric data, the mean was used, and the values were expressed as 95% CIs. P < .05 was considered statistically significant.

Prostate core biopsies from a total of 46 patients were prospectively identified, of whom 31 had biopsies that were positive for adenocarcinoma of the prostate, while 15 had biopsies that showed only benign findings on histologic assessment. Of the 31 cancer cases, 24 were diagnostic biopsies that were performed for evaluation of elevated prostate-specific antigen levels, and the remaining 7 cases (2 of 19 from location 1 and 5 of 12 from location 2) were for active surveillance of previously diagnosed prostate cancer. All procedures were performed by experienced urologists using 18-gauge biopsy needles. Of the 46 cases, 30 (65.2%) were performed under ultrasound guidance, while 16 of 46 (34.8%) were performed using fusion magnetic resonance imaging and ultrasonography. A transperineal approach was used in 29 cases, and a transrectal approach was used in 17 cases. We cumulatively received 535 specimen jars from these patients, with a median of 11 (range: 10–14) specimen jars per case. Of the total 535 specimen jars received, 309 specimen parts (57.8%) had >1 biopsy cores per specimen jar. All PCBs were received in specimen jars filled with 10% formalin with phosphate buffer at a pH of 6.8–7.2 at 25°C (Cardinal Health, Waukegan, Illinois) as fixative. A total of 230 of 535 specimen jars (43%) were received from hospital location 1, of which all were mounted on absorbent nonadherent prepack latex-free Telfa dressing pads. The remaining 305 of 535 (57%) specimen jars were received from hospital location 2, and were freely suspended in formalin-filled jars without mounting on Telfa (Figure 1, A through G). Of these, 22 of 230 (9.5%) specimens from hospital location 1 and 203 of 305 (66.6%) specimens from hospital location 2 had a single core per specimen jar. Of the 535 specimen jars received, 325 (60.8%) were obtained by ultrasound guidance, while the remaining 210 (39.2%) were obtained by fusion imaging. Only 3 of 325 (0.9%) specimens obtained by ultrasound guidance had a single core per jar, compared to 192 of 210 (91.4%) specimens obtained by fusion imaging. There was no difference between the number of cores reported in the procedure notes and the number of cores reported by the grosser when both sets of data were available, as was the case in a majority of cases. There were a few cases where only either number was available and thus this comparison could not be made in those cases, so the number of cores noted in the procedure notes was used.

Figure 1.

Prostate core biopsy submission methods. Single unfragmented (A) and multiple fragmented (B) prostate biopsy cores suspended in formalin-filled specimen jars. Single fragmented (arrowhead) (C) and multiple unfragmented (D and E) and fragmented (arrowhead) (F and G) prostate biopsy cores, some adherent (arrow) to the edges of the Telfa dressing pad.

Figure 1.

Prostate core biopsy submission methods. Single unfragmented (A) and multiple fragmented (B) prostate biopsy cores suspended in formalin-filled specimen jars. Single fragmented (arrowhead) (C) and multiple unfragmented (D and E) and fragmented (arrowhead) (F and G) prostate biopsy cores, some adherent (arrow) to the edges of the Telfa dressing pad.

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On histologic examination, fragmentation of PCBs was observed in 157 of 535 (29.3%) specimen parts. Adenocarcinoma of prostate was identified in 185 of 535 specimen parts (34.6%), of which 113 of 535 (21.1%) were of prognostic grade group ≥2, all with at least some amount of adenocarcinoma of Gleason score 4 and above. Adenocarcinoma was present in 118 of 230 (51.3%) specimen parts received from hospital location 1 compared to 67 of 305 (22%) specimen parts received from hospital location 2. Results of univariate analysis of various parameters in association with PCB fragmentation are provided in the Table. Of all the factors considered, rate of fragmentation was the lowest when a single biopsy core was submitted per specimen jar irrespective of the mounting method (31 of 226; 14% for a single core per jar versus 126 of 309; 41% for >1 core per jar; P < .001) (Figure 2, A and B). For a single core on Telfa, the rate of fragmentation was 5 of 18 (27.8%) compared to 26 of 203 (12.8%) for a single core received unmounted (P = .24). Correlation between rate of fragmentation, number of cores submitted per specimen jar, and mounting method is depicted in Figure 3, A through D.

Figure 2.

Clustered bar graphs displaying correlation between rate of fragmentation and number of cores submitted per specimen jar. Rate of fragmentation was higher when >1 core was submitted per specimen jar compared to when a single core was submitted per specimen jar in both the Telfa-mounted (48% versus 22%; P = .02) (A) and unmounted (27% versus 13%; P = .01) (B) biopsy groups.

Figure 2.

Clustered bar graphs displaying correlation between rate of fragmentation and number of cores submitted per specimen jar. Rate of fragmentation was higher when >1 core was submitted per specimen jar compared to when a single core was submitted per specimen jar in both the Telfa-mounted (48% versus 22%; P = .02) (A) and unmounted (27% versus 13%; P = .01) (B) biopsy groups.

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Figure 3.

Clustered bar graphs showing correlation between rate of fragmentation and specimen mounting method. There was no significant difference in rates of fragmentation between Telfa-mounted and unmounted specimens when 1 (22% versus 13%; P = .24) (A), 2 (50% versus 39%; P = .31) (B), or 4 or more (42% versus 31%; P = .51) (D) biopsy cores were submitted per specimen jar. Rate of fragmentation was significantly higher when 3 biopsy cores were submitted per specimen jar (46% versus 19%; P = .01) (C).

Figure 3.

Clustered bar graphs showing correlation between rate of fragmentation and specimen mounting method. There was no significant difference in rates of fragmentation between Telfa-mounted and unmounted specimens when 1 (22% versus 13%; P = .24) (A), 2 (50% versus 39%; P = .31) (B), or 4 or more (42% versus 31%; P = .51) (D) biopsy cores were submitted per specimen jar. Rate of fragmentation was significantly higher when 3 biopsy cores were submitted per specimen jar (46% versus 19%; P = .01) (C).

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Correlation of Fragmentation Rate of Prostate Core Biopsies With Different Variables on Univariate Analysis

Correlation of Fragmentation Rate of Prostate Core Biopsies With Different Variables on Univariate Analysis
Correlation of Fragmentation Rate of Prostate Core Biopsies With Different Variables on Univariate Analysis

On univariate analysis, the rate of fragmentation was found to be higher when biopsies were mounted on Telfa (104 of 230, 45.2% versus 53 of 305, 17.4%; P < .001), but on multivariate analysis, this association was statistically significant only in the group with 3 cores per specimen jar (32 of 70; 46% mounted fragmented specimens versus 9 of 47; 19% unmounted fragmented specimens; P = .01) (Figure 3, C). Rate of fragmentation correlated with presence of cancer in the cores examined (65 of 185, 35.1% versus 92 of 350, 26.3%; P = .03) when considered together with other variables, but there was no significant difference in fragmentation when this was evaluated independent of number of cores submitted per jar or specimen mounting method. Overall, 125 of 325 (38.5%) specimens obtained by ultrasound guidance showed fragmentation, compared to 32 of 210 (15.2%) specimens obtained by fusion imaging. However, when this was broken down by the number of cores submitted per specimen jar, 122 of 125 (97.6%) fragmented specimens obtained by ultrasound had >1 core per specimen container (P < .001), while only 5 of 210 (2.4%) fragmented specimens obtained by fusion imaging had >1 core submitted per specimen jar (P = .12).

Evaluation of unfragmented core biopsies is crucial for accurate grading and quantification of prostate cancer. Protocols for active surveillance commonly use number of positive cores and/or percentage of core involvement as inclusion criteria. The National Comprehensive Cancer Network guidelines recommend active surveillance when cancer involves <6 out of 12 cores (<50% of core involvement) in patients with prognostic grade groups 1 and 2.7  Fragmentation of biopsy cores can result in erroneous risk stratification and potentially exclude patients from active surveillance protocols. The quantification of cancer on needle core biopsies is also a valuable predictor of the pathologic stage at radical prostatectomy and the outcome after treatment.1–3,7 

The rate of fragmentation in our study was nearly 30% of total biopsy cores received during a period of 1 week. It was therefore our intent to identify modifiable factors that would help decrease the rate of fragmentation. Of the factors investigated, we found that there was an increased likelihood of fragmentation when biopsy cores were (1) submitted with >1 PCB per jar and (2) submitted on absorbent nonadherent dressing pads (Telfa), the latter of which, to our knowledge, has not been previously reported. Telfa dressing pads have been historically used at one of our hospital locations for mounting biopsy specimens before placing them in buffered formalin solution for fixation. Although there is a nonadherent coating on both surfaces of the dressing pad to prevent tissue from clinging to the surface, the edges of the pad lack this property, making tissue prone to adherence. We hypothesize that the increased rate of fragmentation seen with this specimen submission method could be a result of manipulation while picking up delicate biopsy cores with forceps, especially, when they are lodged along the edges of the pad (Figure 1, C through F). A study by Satasivam et al8  compared the rate of fragmentation between 2 prostate biopsy specimen retrieval methods: a “wash” technique where the biopsy cores were directly dislodged into the specimen jar after sampling, and a “swipe” technique where the specimen was swiped onto a piece of paper before transferring to a specimen jar, which appears to be similar to the specimen retrieval method on Telfa dressing pads in our study. They report a significantly lower rate of biopsy core fragmentation in the group using a “wash” technique compared to a “swipe” technique (9.9% versus 21.1; P = .03). They further showed that the rates of fragmentation with the “swipe” technique were similar for cores with benign and malignant histology and suggest that the increased rate of fragmentation could be a result of mechanical force associated with the “swipe” technique.8 

The other factors that were significantly associated with an increased risk of fragmentation was the number of biopsy cores submitted per specimen jar (>1 per jar) and the presence of prostate cancer in the evaluated cores when considered independent of specimen mounting method. These findings are in concordance with findings from previous studies. Fajardo et al6  showed that the mean number of cores per specimen jar (odds ratio [OR] 2.6 versus. 2.1; P = .01) and the number of parts with cancer (OR 6.6 versus 6.2; P <.001) were significantly higher in the group with fragmented biopsy cores than in the group with unfragmented cores. Reis et al5  demonstrated the impact of fragmentation on prostate cancer grading and staging and encouraged the submission of a single biopsy core per specimen jar, which we support based on the findings in the present study. Although the presence of cancer is not a modifiable risk factor, its association is important to consider as it can complicate Gleason scoring and grading of prostate cancer. For example, fragmentation resulted in an overestimation of a number of cores involved by adenocarcinoma, as illustrated in Figure 4, A. In the second case (Figure 4, B), fragmentation resulted in overestimation of the percentage of involved cores, as the smaller fragment showed near complete involvement by adenocarcinoma.

Figure 4.

Hematoxylin and eosin stained whole slide digital images of fragmented prostate core biopsies from representative cases. Adenocarcinoma, Gleason score 4 + 3 = 7 (60% pattern 4), prognostic grade group 3 involving 4 of 5 biopsy cores. Arrows highlight the extent of adenocarcinoma in the involved biopsy cores. This specimen was submitted on a Telfa pad from hospital location 1 as 2 cores by the clinician and counted as 2 cores by the grosser (A). Adenocarcinoma, Gleason score 3 + 3 = 6, prognostic grade group 1 involving 3 of 4 cores and comprising up to 60% of involved cores. Arrows highlight the extent of adenocarcinoma in the involved cores. This specimen was received as 3 freely suspended biopsy cores in a formalin-filled specimen jar from hospital location 2 (B) (original magnifications ×1 [A and B] and ×20 [A and B insets]).

Figure 4.

Hematoxylin and eosin stained whole slide digital images of fragmented prostate core biopsies from representative cases. Adenocarcinoma, Gleason score 4 + 3 = 7 (60% pattern 4), prognostic grade group 3 involving 4 of 5 biopsy cores. Arrows highlight the extent of adenocarcinoma in the involved biopsy cores. This specimen was submitted on a Telfa pad from hospital location 1 as 2 cores by the clinician and counted as 2 cores by the grosser (A). Adenocarcinoma, Gleason score 3 + 3 = 6, prognostic grade group 1 involving 3 of 4 cores and comprising up to 60% of involved cores. Arrows highlight the extent of adenocarcinoma in the involved cores. This specimen was received as 3 freely suspended biopsy cores in a formalin-filled specimen jar from hospital location 2 (B) (original magnifications ×1 [A and B] and ×20 [A and B insets]).

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One of the limitations of the present study was the inability to fully evaluate other potentially controllable factors that may have contributed to biopsy fragmentation, such as the experience of the urologist performing the biopsy and the specimen retrieval technique, due to the small sample size; this may need further investigation in a larger cohort. In conclusion, of the studied factors, the submission of >1 biopsy core per specimen jar and the use of Telfa pads for mounting biopsy specimens are associated with increased biopsy fragmentation. Both factors are easily modifiable practices. Based on our finding, we strongly recommend limiting submission to 1 to 2 biopsy cores per specimen jar and discourage the use of Telfa dressing pads for biopsy specimen mounting to reduce the risk of fragmentation.

The authors would like to acknowledge the team of dedicated urologists: Christopher T. Arrett, MD; Kefu Du, MD; Jason Frankel, MD; Eric H. Kim, MD; Arjun Sivaraman, MD; and Zachary Smith, MD, from the Division of Urologic Surgery at Washington University School of Medicine in St Louis, Missouri.

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Author notes

Kini is currently located at the Department of Pathology, Father Muller Medical College, Mangalore, India. Padmanabhan is currently located at the Department of Pathology and Genomic Medicine, Houston Methodist Hospital,Houston, Texas.

Competing Interests

The authors have no relevant financial interest in the products or companies described in this article.

The project was presented as a poster at the College of American Pathologists annual meeting 2023, Chicago, Illinois, on October 9, 2023.