Purpose The International Ki67 Working Group (IKWG) has developed training for immunohistochemistry (IHC) scoring reproducibility and recommends cut points of ≤ 5% and ≥ 30% for prognosis in ER+, HER2−, stage I/II breast cancer. We examined scoring reproducibility following IKWG training and evaluated these cut points for selecting patients for further testing with the 21-gene Recurrence Score (RS) assay. Methods We included 307 women aged 50+ years with node-negative, ER+PR+HER2− breast cancer and with available RS results. Slides from the diagnostic biopsy were stained for Ki67 and scored using digital image analysis (IA). Two IHC pathologists underwent IKWG training and visually scored slides, blinded to each other and IA readings. Interobserver reproducibility was examined using intraclass correlation (ICC) and Kappa statistics. Results Depending on reader, 8.8–16.0% of our cohort had Ki67 ≤ 5% and 11.4–22.5% had scores ≥ 30%. The ICC for Ki67 scores by the two pathologists was 0.82 (95% CI 0.78–0.85); it was 0.79 (95% CI 0.74–0.83) for pathologist 1 and IA and 0.76 (95% CI 0.71–0.80) for pathologist 2 and IA. For Ki67 scores ≤ 5%, the percentages with RS < 26 were 92.6%, 91.8%, and 90.9% for pathologist 1, pathologist 2, and IA, respectively. For Ki67 scores ≥ 30%, the percentages with RS ≥ 26 were 41.5%, 51.4%, and 27.5%, respectively. Conclusion The IKWG’s Ki67 training resulted in moderate to strong reproducibility across readers but cut points had only moderate overlap with RS cut points, especially for Ki67 ≥ 30% and RS ≥ 26; thus, their clinical utility for a 21-gene assay testing pathway remains unclear.

Supplementary Table 1, Figures 1-10, Methods from An EGFR-ERK-SOX9 Signaling Cascade Links Urothelial Development and Regeneration to Cancer

Supplemental Table 1 and 2. Association of pre-diagnostic BMI, waist circumference, weight change from age 21, total physical activity and vigorous physical activity with telomere length (Supplemental Table 1) and telomere variability (Supplemental Table 2) in cancer cells, stromal cells, basal cells, and luminal epithelial cells in men surgically treated for clinically localized prostate cancer, HPFS.

Background: While substantial evidence indicates that Ki67, a marker of proliferation, is strongly associated with breast cancer outcomes, its clinical utility has been limited given concerns about scoring inter-rater reliability and appropriate cut points. Nonetheless, Ki67 has been used in multiple clinical trials and results from POETIC indicated that low baseline Ki67 (ie, <10%) predicts good prognosis in postmenopausal women with hormone sensitive, early breast cancer. Further, the International Ki67 Working Group (IKWG) has developed website-based training materials to improve reproducibility of Ki67 scoring by immunohistochemistry (IHC) and recently considered the marker to be sufficiently validated to support treatment decisions in early ER+ breast cancer (≤ 5 no chemotherapy, ≥30 chemotherapy indicated). Our aims were to examine Ki67 scoring reproducibility following IKWG training and the extent to which low or high scores could accurately identify patients with low or high 21-gene assay Recurrence Scores (RS) who could selectively avoid this test. Methods: Setting and study population. The study was conducted within Kaiser Permanente Northern California (KPNC), an integrated health care system with over 4.4 million enrollees. We included a random sample of women aged 50+ years at diagnosis of node-negative, ER+PR+HER2- breast cancer with the 21-gene assay done on their surgical specimen from 2018-2020 (n=307). Ki67 staining, training and scoring. We retrieved archived core biopsy specimens, which were sent to NeoGenomics Laboratories, Inc for Ki67 staining and scoring by image analysis (IA) using the hot spot counting method. In addition, two KPNC pathologists specializing in semiquantitative IHC scoring underwent IKWG training and independently scored all slides using the global counting method, blinded to each other and to readings by AI; weighted Ki67 scores were calculated. Analysis. We examined inter-rater reliability across pathologists using intraclass correlation (ICC) and Kappa statistics. We also examined the percent of patients with low Ki67 scores (≤ 5, <10) by each pathologist and by AI who also had low RS (<26) and the percent who had high Ki67 scores (≥30) who also had high RS (≥26). Results: Approximately 83% of patients were ages 50-69 years (median 63), 61% were non-Hispanic white and 93% were stage 1A. The ICC for Ki67 scores (log-transformed) by the two pathologists was 0.82; using a dichotomous cut point of <10 vs ≥10%, the Kappa for the inter-rater reliability was 0.65. Among patients with Ki67 scores of <10% by IA (n=81), pathologist 1 (n=120) or pathologist 2 (n=111), the percent with a RS of <26 was 95.1% for IA, 95.8% for pathologist 1, and 94.6% for pathologist 2. Among patients with Ki67 scores ≤5, the percentages were 90.9%, 92.6% and 91.8% for IA, pathologist 1 and pathologist 2, respectively. Among patients with Ki67 scores ≥30 by AI (n=69), pathologist 1 (n=41) or pathologist 2 (n=35), the percent who had a RS ≥26 was 27.5% for IA, 41.5% for pathologist 1 and 51.4% for pathologist 2. Results are improved if we exclude all 50 patients with weak PR by IHC (1-10%); for example, among patients with Ki67 scores of <10%, the percent with a RS of <26 was 97.1% for IA, 98.1% for pathologist 1, and 97.9% for pathologist 2. Conclusion: Among women aged 50+ years with node-negative, ER+PR+HER2- breast cancer in our setting, approximately 5-10% of patients with Ki67 scores of ≤ 5% or <10% on core biopsies would have high RS (≥26) on surgical specimens and over 48% of cases with Ki67 scores ≥30 would have low RS (<26), which may be insufficiently accurate for avoiding the 21-gene or other multi-gene assays. Future studies are needed to examine whether restricting Ki67 testing to ER+HER2- patients with PR >10% would improve its clinical validity. Citation Format: Veronica C. Shim, Robin J Baker, Wen Jing, Sally S Agersborg, Thomas K Lee, Wamda Goreal, Ninah Achacoso, Catherine Lee, Marvella Villasenor, Amy Lin, Malathy Kapali, Laurel A Habel. Ki67 assessment based on international Ki67 working group recommendations and correlation with 21-gene assay results in a large integrated health care system: We might not be there yet [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-10.

Mitotic rate is an important prognostic predictor in invasive breast carcinoma. Current guidelines recommend counting mitoses from 10 contiguous high power fields (HPFs) in the core biopsy. We propose a method to score mitotic activity in 1 HPF at the most mitotically active area of the tumour edge, or the interface between invasive tumour and benign breast tissue. We propose a score of 1, 2, or 3, corresponding to ≤1, 2, or ≥3 mitoses in 1 HPF, respectively. A total of 141 breast core biopsies with corresponding surgical excisions were blindly examined. We counted the number of mitotic figures in 1 HPF and in 10 contiguous HPFs in the core biopsy and compared with the mitotic count from 10 contiguous HPFs in the excision which is considered the gold standard. Concordance rates and interobserver agreement rates were calculated. The concordance rate was 82.3%, 78.7% and 82.3% between 1 HPF versus 10 HPFs in the core biopsy, 1 HPF in the core biopsy versus 10 HPFs in the excision and 10 HPFs in the core biopsy vs 10 HPFs in the excision, respectively. In the core biopsy, all three investigators agreed in 73.8% and 83.7% of the cases using the 1 HPF method and the 10 HPFs method, respectively; in the excision specimen, agreement was reached in 82.3% of the cases. The 1 HPF method showed similar concordance rate and interobserver agreement compared to the conventional method in the prediction of the mitotic score in the excision in all score groups. When stratified by mitotic score, the 1 HPF method predicted superior correlation with excision in the score 1 group than the 10 HPFs method, but not in the score 2 or 3 groups. From these findings we conclude that the proposed 1 HPF method can be used in clinical practice to grade invasive breast carcinomas in core biopsies, with the possibility of being utilised in small biopsies with less than 10 HPFs of invasive carcinoma.

Congenital Morgagni hernia (CMH) is a rare congenital anomaly is typically diagnosed in childhood and on occasions in adults during work up of unexplained respiratory infections or gastrointestinal symptoms. The average age of laparoscopic repair of CMH was 3.3 years. We describe a newborn with fetal aberrant ductus venosus with progressive right ventricular dilation prompting early delivery. Post-natally, the baby had frequent episodes of cyanosis. Echocardiogram during distress showed compression of the inferior vena cava and of the right heart, with significant right to left shunt through patent foramen ovale. Infant underwent successful laparoscopic diaphragmatic hernia repair with resolution in her episodes of cyanosis.

OBJECTIVE:To determine if targeted and modulated radiofrequency ablation (RFA) of the urinary bladder using our novel ablation device (Denerblate) reduces bladder nerve density, potentially leading to a novel strategy for the management of overactive bladder. METHODS:Fifteen pigs were divided into 4 groups: control (n = 3), 1-week (n = 4), 4-week (n = 4) and 12-week (n = 4) survival times. Denerblate was deployed on the trigone area of the bladder. Three 240-second cycles of modulated RFA were applied with 30 seconds between cycles. At the end of each survival term, urinary bladders were harvested for histopathologic evaluation. Nerve count and density were manually calculated. RESULTS:All procedures were successfully completed, and all animals survived to the desired time points. Mean nerve density (nerves/mm2) was highest in the control and 1-week survival group compared to the 4-week and 12-week groups, both of which demonstrated significant diminishment. Nerve density in the bladder neck at control, 1 week, 4 weeks, and 12 weeks were 1.8, 1.35, 0.87, and 0.12, respectively (P <.001). Nerve density in the bladder trigone area at control, 1 week, 4 weeks, and 12 weeks were 1.5, 0.98, 0.65, and 0.112, respectively (P <.001). Epithelial heat injury was observed in 14.3% at 1 week, 10.7% at 4 weeks, but completely resolved by 12 weeks. CONCLUSION:In the porcine model, modulated RFA delivered by our novel device reduced nerve density in the bladder neck and trigone by 88.6% and 88.9% at 12 weeks without evidence of lasting epithelial injury.

Introduction and Objectives: Laser endoscopic X-ray-guided intrarenal tract (LEXIT) is a recently described holmium laser retrograde access technique for creating percutaneous access during a percutaneous nephrolithotomy. We compared bleeding, ease of access, and the time to achieve access for each of the following three modalities: LEXIT, retrograde Lawson puncture wire, and antegrade 18-gauge nephrostomy needle access in the porcine kidney. Methods: Eight pigs underwent an average of five nephrostomy accesses per kidney under simultaneous laparoscopic vision at 5 mm Hg insufflation pressure. Data collected included: access time (seconds), bleeding intensity (scale: 1 [no bleeding] - 10 [severe bleeding]), bleeding duration (seconds), accuracy of caliceal entry, and surgeon comfort with the technique (scale: 1 [very easy] - 10 [very difficult]). Results: A total of 64 nephrostomy accesses were obtained. The speed of nephrostomy access with LEXIT was significantly faster than the nephrostomy needle and Lawson wire (p < 0.001). Bleeding intensity (p = 0.002) and severity (p = 0.001) were lower with the Lawson puncture wire, followed by LEXIT and then by the nephrostomy needle. LEXIT was rated as easier in acquiring access within the upper pole (p = 0.003) and interpolar calices (p < 0.001). Histopathology demonstrated no difference in parenchymal damage between LEXIT and nephrostomy needle (p = 0.18); however, LEXIT was associated with significantly increased peri-tract thermal injury, although within a narrow focus of 1.6 mm (p < 0.01). Conclusion: Among the three renal access techniques, LEXIT provided the fastest access times and greatest ease of access specifically for upper pole and interpolar calices. Also, bleeding with LEXIT was significantly less compared with the standard antegrade nephrostomy needle access. Histopathological analysis demonstrated that the holmium laser resulted in focal thermal tissue effects similar in range to the blunt tissue trauma caused by the 18-gauge nephrostomy needle.

OBJECTIVES:Checkpoint inhibitors are approved for the treatment of urothelial bladder cancer. However, there have been no reports on the prognostic value of programmed-death receptor ligand 1 (PD-L1) expression in squamous cell carcinoma (SCC) of the bladder. We assessed the relationship between PD-L1 expression, clinicopathological features, and oncologic outcomes in bladder SCC. METHODS AND MATERIALS:Immunohistochemistry of PD-L1 was performed on 151 radical cystectomy specimens with pure SCC treated in Mansoura, Egypt from 1997 to 2004. RESULTS:Median patient age was 52 years (range: 36-74 years) and median length of follow up was 63 months (range: 1-100 months). Schistosomiasis was present in 81% of the specimens and 93% had muscle-invasive disease on pathologic staging. PD-L1 expression was negative in 50 (33%) of the specimens. Negative PD-L1 expression was associated with higher pathologic tumor stage (P = 0.04), higher grade lesions (P = 0.01), and the presence of lymphovascular invasion (P < 0.01). Kaplan-Meier analyses showed that negative PD-L1 expression is associated with worse recurrence-free (P = 0.01) and worse cancer-specific survival (P = 0.01). Multivariable Cox regression analyses showed negative PD-L1 expression was an independent predictor of disease recurrence (hazards ratio 2.05, 95% confidence interval 1.06-3.96, P = 0.03) and cancer-specific mortality (hazards ratio 2.89, 95% confidence interval 1.22-6.82, P = 0.02). CONCLUSIONS:Negative PD-L1 expression is associated with higher pathologic tumor stage, higher grade lesions, presence of lymphovascular invasion, and worse oncologic outcomes after radical cystectomy for SCC. These findings support the need for the inclusion of patients with bladder SCC into immunotherapy clinical trials.

You have accessJournal of UrologyStone Disease: Surgical Therapy VI (MP79)1 Apr 2019MP79-06 COMPARISON OF NEPHROSTOMY TECHNIQUES IN THE PORCINE KIDNEY: RETROGRADE LASER ENDOSCOPIC X-RAY-GUIDED INTRARENAL TRACT (LEXIT) VERSUS RETROGRADE LAWSON ROCKET WIRE ACCESS VERSUS STANDARD NEPHROSTOMY NEEDLE ANTEGRADE ACCESS Kamaljot Kaler*, Vinay Cooper, Mitchell O'Leary, Zachary Valley, Thomas Lee, Roshan Patel, Jaime Landman, and Ralph Clayman Kamaljot Kaler*Kamaljot Kaler* More articles by this author , Vinay CooperVinay Cooper More articles by this author , Mitchell O'LearyMitchell O'Leary More articles by this author , Zachary ValleyZachary Valley More articles by this author , Thomas LeeThomas Lee More articles by this author , Roshan PatelRoshan Patel More articles by this author , Jaime LandmanJaime Landman More articles by this author , and Ralph ClaymanRalph Clayman More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000557358.67766.baAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Laser Endoscopic X-ray-guided Intrarenal Tract (LEXIT) is a recently described retrograde access technique for creating a percutaneous nephrostomy using the Holmium laser. Herein, we compared the feasibility and safety of LEXIT with the retrograde Lawson rocket wire technique and standard antegrade 18-gauge nephrostomy needle access in a porcine kidney. METHODS: Seven pigs underwent nephrostomy accesses with simultaneous laparoscopic vision at 5 mmHg pressure. For each kidney, the aforementioned three access methods were randomized. The following data were collected: access time, bleeding severity (Scale: 1=no bleeding – 10=severe bleeding), bleeding duration, calyceal point of entry, and surgeon comfort with the technique (Scale: 1=very easy - 10=very difficult). Analysis of variance was performed to examine the differences among the 3 access methods. RESULTS: A total of 73 accesses were completed with an average of five nephrostomy tracts per kidney. The LEXIT access time was significantly faster than the nephrostomy needle or Lawson puncture wire (8.4, 63, 21 seconds (s), respectively, p<0.002). Bleeding intensity and duration were significantly lower with the Lawson wire (0.0, 0.0 s), versus LEXIT (2.1, 58.6 s) and the nephrostomy needle (3.4, 110.5 s) (Table 1). LEXIT was rated as in the easiest method for acquiring access within all calyces: upper pole (p=0.003), interpolar calyces (p<0.001), and lower pole (p<0.006) (Table 2). CONCLUSIONS: In the in vivo porcine kidney, endoscopic-guided retrograde holmium Laser Endoscopic X-ray-guided Intrarenal Tract (LEXIT) creation provided the fastest access times and greatest ease of access to the upper and interpolar calyces. Bleeding during LEXIT was significantly less than standard antegrade nephrostomy needle access. Source of Funding: none Calgary, Canada; Orange, CA© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e1153-e1154 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kamaljot Kaler* More articles by this author Vinay Cooper More articles by this author Mitchell O'Leary More articles by this author Zachary Valley More articles by this author Thomas Lee More articles by this author Roshan Patel More articles by this author Jaime Landman More articles by this author Ralph Clayman More articles by this author Expand All Advertisement PDF downloadLoading ...

INTRODUCTION:We evaluated and compared five currently available energy-based vessel sealing devices to assess typical surgical metrics. METHODS:We tested Caiman 5 (C5), Harmonic Scalpel Ace Plus (HA), Harmonic Ace +7 (HA7), LigaSure (LS), and Enseal G2 (ES) on small (2-5 mm), medium (5.1-7 mm), and large (7.1-9 mm) vessels obtained from 15 Yorkshire pigs. Vessels were randomly sealed and transected. We recorded sealing and transection time, charring and carbonization, thermal spread, and bursting pressure (BP). Specimens were sent for histopathologic evaluation of seal quality and thermal spread. RESULTS:A total of 246 vessels were evaluated: 125 were arteries and 121 were veins. There was no difference in BPs for small size arteries. For medium arteries, C5 provided the highest BP (proximal and distal jaw), followed by HA7, ES, LS, and HA [1740, 1600, 1165, 1165, 981, and 571 mm Hg, respectively, HA250 mm Hg.

CONTEXT - The presence of cribriform glands/ducts in the prostate can pose a diagnostic challenge. Cribriform glands/ducts include a spectrum of lesions, from benign to malignant, with vastly different clinical, prognostic, and treatment implications. OBJECTIVE - To highlight the diagnostic features of several entities with a common theme of cribriform architecture. We emphasize the importance of distinguishing among benign entities such as cribriform changes and premalignant to malignant entities such as high-grade prostatic intraepithelial neoplasia, atypical intraductal cribriform proliferation, intraductal carcinoma of the prostate, and invasive adenocarcinoma (acinar and ductal types). The diagnostic criteria, differential diagnosis, and clinical implications of these cribriform lesions are discussed. DATA SOURCES - Literature review of pertinent publications in PubMed up to calendar year 2017. Photomicrographs obtained from cases at the University of California at Irvine and authors' collections. CONCLUSIONS - Although relatively uncommon compared with small acinar lesions (microacinar carcinoma and small gland carcinoma mimickers), large cribriform lesions are increasingly recognized and have become clinically and pathologically important. The spectrum of cribriform lesions includes benign, premalignant, and malignant lesions, and differentiating them can often be subtle and difficult. Intraductal carcinoma of the prostate in particular is independently associated with worse prognosis, and its presence in isolation should prompt definitive treatment. Patients with atypical intraductal cribriform proliferation, intraductal carcinoma of the prostate, or even focal cribriform pattern of invasive adenocarcinoma in biopsies would not be ideal candidates for active surveillance because of the high risk of adverse pathologic findings associated with these entities.

Non-small cell lung cancer (NSCLC) has emerged as a paradigm for clinical application of precision medicine as optimal therapy is commonly chosen based on genomic biomarkers identified in a patient's tumor sample. Recurrent driver alterations are well described, however, a need to continually identify rare variants remains clinically relevant. We identified an incident case of advanced NSCLC with a PDGFR-α N848 K activation loop mutation with no other concurrent oncogenic drivers. Amino acid sequence alignment confirmed homology to the imatinib-sensitive KIT N822 K activation loop mutation observed in GIST. The patient achieved a 2-year response to single agent imatinib that is ongoing. While PDGFR-α N848 K is rare among public sequencing databases our cases strongly suggests functional relevance and highlights the importance of studying rare variants in NSCLC.

Diffusion-weighted imaging (DWI) is an increasingly utilized sequence in the assessment of abdominal and pelvic lesions. Benign lesions containing hemorrhagic products, with conglomerates of tightly packed blood cells or fibers, can have restricted water diffusion on DWI and apparent diffusion coefficient maps. Such lesions can have restricted diffusion erroneously attributed to malignancy. This review illustrates benign hemorrhagic lesions displaying restricted diffusion, with histopathologic correlation in relevant cases.

Current and recent smoking have been associated with a greater risk of prostate cancer recurrence and mortality, though the underlying mechanism is unknown.

Paragangliomas are rare neoplasms that arise from the chromaffin cells of the autonomic nervous system. Although paragangliomas can occur anywhere paraganglia are present, they tend to occur in the head, neck, and retroperitoneum. Rarely, paragangliomas can occur in the peripancreatic area and present as a pancreatic mass, creating a diagnostic challenge for the clinician, radiologist, and pathologist. Here, we present a case of a 70-year-old woman with history of breast carcinoma who presented with chronic constipation, early satiety, and an abdominal mass. Her first abdominal CT described a 3.6 cm × 5 cm × 4.5 cm cystic and solid mass involving the pancreatic tail that was suspicious for a pancreatic neoplasm. A subsequent abdominal CT described a 5.9 cm multilobulated solid and cystic lesion close to the pancreatic tail. Endoscopic ultrasound-guided fine-needle aspirate of the mass demonstrated scant to moderate cellularity of a heterogeneous population of atypical cells, some with epithelioid morphology and others appearing neuroendocrine-like. By morphology and immunohistochemical stains, an extra-adrenal paraganglioma or pheochromocytoma was considered as a possible diagnosis. The surgical resection specimen confirmed the diagnosis of paraganglioma. This case demonstrates the importance of awareness of paragangliomas in the differential diagnosis of a fine-needle aspiration of a pancreatic mass to avoid erroneous diagnosis.

OBJECTIVE To compare the performance of 3 contemporary ureteroscopic biopsy devices for the histopathologic diagnosis of upper tract urothelial carcinoma (UTUC). METHODS We retrospectively reviewed 145 patients who underwent 182 urothelial biopsies using 2.4F backloaded cup biopsy forceps, a nitinol basket, or 3F standard cup biopsy forceps at 3 tertiary academic centers between 2011 and 2016. Experienced genitourinary pathologists provided an assessment of each specimen without knowledge of the device used for biopsy. For patients who underwent nephroureterectomy without neoadjuvant chemotherapy within 3 months of biopsyproven UTUC diagnosis, the biopsy grade was compared with both the grade and stage of the surgical specimen. RESULTS Biopsy utilization varied among the 3 institutions (P < .0001). Significant variabilities in specimen size (P = .001), the presence of intact urothelium (P = .008), and crush artifact (P = .028) were found among the biopsy devices. The quality of specimens from backloaded cup forceps was rated similarly to the nitinol basket (P > .05) and was favored over standard cup forceps specimens. Grade concordance was not affected by specimen size (P > .05), morphology (P > .1), or location (P > .5). No difference existed among the devices in the rate of acquiring a grade concordant biopsy; however, the backloaded cup forceps provided concordant biopsies that could be distinguished as low-and high-grade (P = .02). CONCLUSION The backloaded cup forceps and nitinol basket obtained a higher quality urothelial specimen compared with standard cup forceps. Ureteroscopic biopsy device selection did not significantly impact the accuracy of the histologic diagnosis of UTUC. (C) 2018 Elsevier Inc.

BACKGROUND Metastatic recurrence after treatment for locoregional cancer is a major cause of morbidity and cancer-specific mortality. Distinguishing metastatic recurrence from the development of a second primary cancer has important prognostic and therapeutic value and represents a difficult clinical scenario. Advances beyond histopathological comparison are needed. We sought to interrogate the ability of comprehensive genomic profiling (CGP) to aid in distinguishing between these clinical scenarios. MATERIALS AND METHODS We identified three prospective cases of recurrent tumors in patients previously treated for localized cancers in which histologic analyses suggested subsequent development of a distinct second primary. Paired samples from the original primary and recurrent tumor were subjected to hybrid capture next-generation sequencing-based CGP to identify base pair substitutions, insertions, deletions, copy number alterations (CNA), and chromosomal rearrangements. Genomic profiles between paired samples were compared using previously established statistical clonality assessment software to gauge relatedness beyond global CGP similarities. RESULTS A high degree of similarity was observed among genomic profiles from morphologically distinct primary and recurrent tumors. Genomic information suggested reclassification as recurrent metastatic disease, and patients received therapy for metastatic disease based on the molecular determination. CONCLUSIONS Our cases demonstrate an important adjunct role for CGP technologies in separating metastatic recurrence from development of a second primary cancer. Larger series are needed to confirm our observations, but comparative CGP may be considered in patients for whom distinguishing metastatic recurrence from a second primary would alter the therapeutic approach. The Oncologist 2017;22:152-157Implications for Practice: Distinguishing a metastatic recurrence from a second primary cancer can represent a difficult clinicopathologic problem but has important prognostic and therapeutic implications. Approaches to aid histologic analysis may improve clinician and pathologist confidence in this increasingly common clinical scenario. Our series provides early support for incorporating paired comprehensive genomic profiling in clinical situations in which determination of metastatic recurrence versus a distinct second primary cancer would influence patient management.