Original Pathology Reports Research Articles

Uterine corpus invasion in cervical cancer: a multicenter retrospective case-control study.

To determine the accuracy of uterine corpus invasion (UCI) diagnosis in patients with cervical cancer and identity risk factors for UCI and depth of invasion. Clinical data of patients with cervical cancer who underwent hysterectomy between 2004 and 2016 were retrospectively reviewed. UCI was assessed on uterine pathology. Independent risk factors for UCI and depth of invasion were identified using binary and ordinal logistic regression models, respectively. A total of 2,212 patients with cervical cancer from 11 medical institutions in China were included in this study. Of these, 497 patients had cervical cancer and UCI, and 1,715 patients had cervical cancer and no UCI, according to the original pathology reports. Retrospective review of the original pathology reports revealed a missed diagnosis of UCI in 54 (10.5%) patients and a misdiagnosis in 36 (2.1%) patients. Therefore, 515 patients with cervical cancer and UCI (160 patients with endometrial invasion, 176 patients with myometrial invasion < 50%, and 179 patients with myometrial invasion ≥ 50%), and 1697 patients with cervical cancer without UCI were included in the analysis. Older age, advanced stage, tumor size, adenocarcinoma, parametrial involvement, resection margin involvement, and lymph node metastasis were independent risk factors for UCI. These risk factors, except resection margin involvement, were independently associated with depth of UCI. UCI may be missed or misdiagnosed in patients with cervical cancer on postoperative pathological examination. Older age, advanced stage, tumor size, adenocarcinoma, parametrial involvement, resection margin involvement, and lymph node metastasis were independent risk factors for UCI and depth of UCI, with the exception of resection margin involvement.

Interobserver reproducibility of perineural invasion of prostatic adenocarcinoma in needle biopsies

Numerous studies have shown a correlation between perineural invasion (PNI) in prostate biopsies and outcome. The reporting of PNI varies widely in the literature. While the interobserver variability of prostate cancer grading has been studied extensively, less is known regarding the reproducibility of PNI. A total of 212 biopsy cores from a population-based screening trial were included in this study (106 with and 106 without PNI according to the original pathology reports). The glass slides were scanned and circulated among four pathologists with a special interest in urological pathology for assessment of PNI. Discordant cases were stained by immunohistochemistry for S-100 protein. PNI was diagnosed by all four observers in 34.0% of cases, while 41.5% were considered to be negative for PNI. In 24.5% of cases, there was a disagreement between the observers. The kappa for interobserver variability was 0.67–0.75 (mean 0.73). The observations from one participant were compared with data from the original reports, and a kappa for intraobserver variability of 0.87 was achieved. Based on immunohistochemical findings among discordant cases, 88.6% had PNI while 11.4% did not. The most common diagnostic pitfall was the presence of bundles of stroma or smooth muscle. It was noted in a few cases that collagenous micronodules could be mistaken for a nerve. The distance between cancer and nerve was another cause of disagreement. Although the results suggest that the reproducibility of PNI may be greater than that of prostate cancer grading, there is still a need for improvement and standardization.

Diagnosing nonalcoholic fatty liver disease in patients with intrahepatic cholangiocarcinoma: pitfalls of imaging and pathologic criteria

Presenter: Thomas Sutton MD | Oregon Health and Science University Background: Intrahepatic cholangiocarcinoma (ICC) is increasing in incidence and is potentially associated with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). The presence of both NAFLD and NASH has been shown to affect overall survival in patients with resected ICC. Steatosis, the primary criterion for NAFLD/NASH, may be under-reported on pathology and imaging, potentially impacting epidemiologic conclusions used to guide high-risk screening and treatment recommendations for ICC. We sought to evaluate the performance of standard-of-care (SOC) pathology, computed tomography (CT), and magnetic resonance imaging (MRI) for identifying steatosis. Methods: We identified n=52 patients with ICC treated with curative-intent resection from 2004-17. Hepatobiliary pathologists and radiologists specifically re-reviewed areas of non-malignant liver on tissue sections and pre-operative imaging, respectively, for evidence of steatosis. The pathologic criterion for steatosis was >5% of surface area involved by steatosis as evaluated by low to medium power examination. For MRI, chemical shift artifact seen on standard in and out-of-phase T1-weighted imaging was utilized to identify steatosis. For CT, density measurements were utilized, either absolute measurements on non-contrast CT or relative densities between liver and spleen when only post-contrast portal venous phase images were available. Using the dedicated pathology re-review as the reference, the accuracy of SOC pathology, contrasted CT, and MRI for diagnosing steatosis was evaluated by receiver operating characteristics (ROC) analysis. Results: The median patient age was 64-years with an equal gender distribution. The median body mass index was 30.3 kg/m2, and 11 (21%) patients had diabetes mellitus. Dedicated pathology review identified steatosis in 20 patients (38%) and was discordant from original reports in 8 cases (15%), with 4 instances each of over-diagnosis and under-diagnosis. On ROC analysis, the original pathology report correctly identified steatosis with an area under the curve (AUC) of 0.87 (P < 0.001 compared to chance), while MRI had an AUC of 0.83 (P < 0.001). Dedicated CT review was less accurate for steatosis (AUC 0.65, P=0.01), and SOC CT was not significantly better than chance (AUC 0.58, P=0.5)(Figure). Conclusion: SOC imaging, SOC pathologic examination, and dedicated review of imaging are less accurate in the diagnosis of steatosis compared to dedicated pathologic review of non-malignant liver tissue. The authors suspect this could be due to the lack of emphasis on documenting steatosis by pathologists and radiologists in cases of malignancy, where documenting cancer-associated features is understandably the primary focus. Epidemiologic studies relying on SOC imaging reports, and to a lesser extent those relying on SOC pathology or dedicated imaging review, are limited in their validity when associating NAFLD with primary liver cancers such as ICC and should be interpreted with caution.

Prognostic Significance of HER2 Expression Changes Following Neoadjuvant Chemotherapy in Saudi Patients With Locally Advanced Breast Cancer

BackgroundProgesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) significantly influence disease prognosis and therapeutic response in patients with breast cancer. Neoadjuvant chemotherapy (NACT) can change the receptor status, affecting the disease characteristics. Patients and MethodsA retrospective chart review was carried out at a single tertiary care hospital in Riyadh, Kingdom of Saudi Arabia, from December 2008 to December 2014, where 91 adult female patients diagnosed with locally advanced breast cancer planning to receive NACT were included. Original pathology and surgical histopathology reports were assessed, and patients were followed up to recurrence, death, or until December 2019. An expression for the ER, PR, and HER2 was carried out in pre and post NACT specimens by an experienced pathologist, and all HER2 with 2+ immunohistochemistry was sent for fluorescence in situ hybridization as per American Society of Clinical Oncology guidelines. ResultsER pre- and postoperatively changed from positive to negative in 17.6% of patients and from negative to positive in 1.1% of patients (P < .001). ER status remained stable in 81.3% of patients. PR changed from positive to negative in 13.2% of patients, and from negative to positive in 3.3% of patients (P < .001), whereas it remained stable in 83.5% of patients. HER2 changed from positive to negative in 11% of patients, and from negative to positive in 5.5% of patients (P < .001), and it remained stable in 83.5% of patients. No significant association was found between overall survival and disease-free-survival with HER2 expression change. ConclusionNACT can induce changes in the ER, PR, and HER2 status, which should be evaluated post-NACT to choose the optimal treatment regimens.

A Journey Through 100 Years of Vestibular Schwannoma Surgery at Mayo Clinic: A Historical Illustrative Case Series.

: The present state of vestibular schwannoma (VS) management is the product of over a century of technical progress by revolutionary surgeons who transformed a once perilous operation. At the beginning of the 1900s, patients who did not succumb to their disease were treated exclusively with surgery, which itself was almost assuredly devastating. Through the pioneering work of surgeons such as Harvey Cushing, Walter Dandy, William House, and others, safer surgical approaches were established with concurrent advances in neuromonitoring, neuroanesthesia, radiology, and adoption of the operating microscope. Owing to refinements in radiosurgical treatment and a greater understanding of the natural history of disease, there has been a dramatic shift toward more conservative management in recent years. For more than 100 years, the Mayo Clinic in Rochester, MN, has maintained an active and uninterrupted VS practice with activities that are well documented and preserved through the Mayo Clinic historical archives. We herein report representative early cases to illustrate the fascinating evolution in VS surgery over the past century at a single-tertiary referral center. Original clinical, imaging, pathology, and operative reports are presented from each era of management. To accurately portray the medical context of each era, antiquated terminology is intentionally preserved as originally transcribed.

Correlation between modified Magee equation-2 and Oncotype-Dx recurrence scores using both traditional and TAILORx cutoffs and the clinical application of the Magee Decision Algorithm: a single institutional review.

Oncotype Dx (ODX) is used to predict recurrence risk for estrogen-positive (ER +), HER2-negative and lymph node negative breast cancer, however, due to the cost its use maybe limited in low-resource areas. The aim of this study is to assess the concordance between the modified Magee Equation-2 (MME-2) and ODX recurrence scores (RS). The secondary aim is to apply the Magee Decision Algorithm (MDA) using the MME-2 to determine which patients are unlikely to benefit from ODX testing. All newly diagnosed ER + , HER2 negative, lymph node negative breast cancer patients with available ODX-RS from 2008-2018 were included. The original pathology reports were reviewed and chart review was performed. The MME-2 scores were calculated and correlated with the ODX-RS. The MDA was applied to our cohort to assess which patients would not benefit from ODX testing. A total of 579 patients were included. There was an overall moderate correlation between ODX-RS and MME-2 score (Pearson correlation coefficient = 0.635). The overall concordance between ODX and MME-2 scores was similar when using both the traditional and TAILORx cutoffs (63.3% vs. 63.7%, respectively). Applying the MDA, for patients with MME-2 scores < 18, 96.8% of patients had the expected ODX-RS of < 25. For patients with MME-2 RS > 30, 90% had the expected ODX-RS of > 25. Concordance was highest in the high-risk category using both cutoffs. For patients with MME-2 18-25 and a mitotic score of 1, 88.8% had the expected ODX-RS of > 25. There is a moderate correlation between MME-2 score and ODX-RS. The overall concordance was similar for both traditional and TAILORx cutoffs. The strongest concordance was found in the high-risk category for both cutoffs. The MME-2 can be used to identify patients unlikely to benefit from ODX testing using the MDA.

Influence of uterine corpus invasion on prognosis in stage IA2–IIB cervical cancer: A multicenter retrospective cohort study

ObjectiveTo determine the associations between the presence and depth of uterine corpus invasion and survival in patients with cervical cancer. MethodsClinical data of patients with stage IA2–IIB cervical cancer who underwent radical hysterectomy between 2004 and 2016 were retrospectively reviewed. Uterine corpus invasion was identified from a review of uterine pathology. Independent prognostic factors for 5-year disease-free survival (DFS) and overall survival (OS) were identified using multivariate forward stepwise Cox proportional hazards regression models. ResultsA total of 1414 patients with stage IA2–IIB cervical cancer from 11 medical institutions in China were included. Retrospective review of the original pathology reports revealed a missed diagnosis of uterine corpus invasion in 38 (13.4%) patients and a misdiagnosis in 20 (1.8%) patients. Therefore, 284 patients with cervical cancer and uterine corpus invasion (90 [31.7%] patients had endometrial invasion, 105 [37.0%] patients had myometrial invasion <50%, and 89 [31.3%] patients had myometrial invasion ≥50%), and 1130 patients with cervical cancer without uterine corpus invasion were included in the analysis. The 5-year DFS and OS were significantly shorter for patients with uterine corpus invasion compared to patients with no uterine corpus invasion. Myometrial invasion ≥50% was an independent prognostic factor associated with decreased 5-year DFS (aHR, 2.307, 95% CI, 1.588–3.351) and 5-year OS (aHR, 2.736, 95% CI, 1.813–4.130), while myometrial invasion <50% or endometrial invasion had no effect on patient outcomes. ConclusionsDiagnosis of uterine corpus invasion is frequently missed. Myometrial invasion ≥50% within the uterine corpus was an independent factor associated with worse prognosis in patients with cervical cancer, while myometrial invasion <50% or endometrial invasion had no effect on outcomes.

Surgical Complications and Referral Patterns in 567 Patients with Differentiated Thyroid Cancer in the Northern Region of the Netherlands: A Population-Based Study Towards Clinical Management Implementation

BackgroundIn the Netherlands, differentiated thyroid cancer (DTC) is treated surgically in three different hospital types, including university, teaching, and non- teaching peripheral hospitals. This study evaluates postoperative complications and referral patterns in patients with DTC in the northern region of the Netherlands to gain an understanding on how to improve management implementation.MethodsData from 567 patients diagnosed between 1989 and 2009 were obtained from the Netherlands Cancer Registry and were supplemented with information from hospital digital information systems and patient records from 15 hospitals: 1 university, 3 teaching, and 11 peripheral hospitals. Surgically treated patients with a histologically proven DTC derived from the original pathology reports were included.ResultsSurgical treatment could be performed in a single procedure in 234 patients (41.3%), but several surgeries were needed in the remaining 333 patients (58.7%). Recurrent laryngeal nerve (RLN) palsy occurred after all types of thyroid surgical procedures, but mostly after initial (hemi)thyroidectomy and reoperations. RLN was temporary in 3.2% of the nerves at risk and persistent in 1.8%. Temporary hypocalcemia developed in 13.7% of patients, and persistent hypocalcemia occurred in 4.8%. Patients were mainly referred to the university hospital from a non-teaching (40.7%, 48/118) or teaching hospital (11.1%, 16/144); however, 80% of patients were not referred.ConclusionsThe complication rate and number of multiple surgeries support the efforts in optimizing clinical management in thyroid cancer. Careful considerations prior to initial surgical treatment by early discussion in telemedicine-based regional tumor boards could possibly prevent reoperations and potentially diminish complications.

Abstract P3-08-35: Reassessment of traditional oncotype scoring using TAILORx criteria: A large institutional review

Abstract Background. Oncotype Dx Recurrence Score (RS) is a 21-gene assay used to predict recurrence in early stage breast cancer and guide chemotherapy decisions. After the completion of the TAILORx trial in 2017, there were changes in the cutoffs for the risk categories and found that there was chemotherapy benefit for women age &amp;lt;50 and RS 16-25. The aim of this study was to re-categorize patients using the TAILORx cutoffs and reassess clinical outcome based on recurrence and metastasis.Materials and Methods. With IRB approval, the CoPath pathology database was queried for patients who were newly diagnosed with breast cancer from 2012 to 2017 and Oncotype scores. The original pathology report and chart was reviewed to assess treatment decisions, recurrences and/or metastasis and their follow-up. Patients with hormone receptor negative, HER2 positive or lymph node macrometastasis were excluded. The patient were re-categorized based on TAILORx cutoffs and subgroup analysis was performed based on age, RS, recurrences and metastasis.Results. There was a total of 620 patients. The mean age was 60.19 years (range, 25-81 years). The mean follow-up was 36.67 months (0-262 months). Forty-seven patients were added to the high-risk category based on the lower TAILORx cutoff (recurrence scores =26-30). An additional 56 patients were recommended chemotherapy based on RS 16-25 and age &amp;lt;50. Recurrence was present in 26/620 patients. The recurrence rate was higher in younger patients (age &amp;lt;50) (8% vs 3.4%, p=0.033) and also higher in patients who refused chemotherapy than the patients who received chemotherapy (13% vs 6%, p=0.013). The recurrence rate was lower in patients who received hormonal therapy (2.4% vs 5%, p=0.007). When the patients were stratified based on age and RS, younger patients who refused chemotherapy with higher RS (&amp;gt; 16) showed even higher recurrence than those who received chemotherapy (33% vs 6%). The older patients with higher RS (&amp;gt; 25) showed no significant difference for recurrence between the group who received chemotherapy and who did not receive/refuse chemotherapy. There was a total of 17/620 patients with metastasis. It was frequent in younger patients (age &amp;lt;50) and higher tumor grade (p=0.014 and 0.032, respectively). There was no significant difference for metastasis in patients who received or did not receive/refused chemotherapy. Interestingly, there were no metastasis in 11 old patients with higher RS &amp;gt;25) who refused chemotherapy. Conclusion. Based on the TAILORx trial recommendations, the number of patients receiving chemotherapy almost tripled in our cohort. The recurrence and metastatic rate were more frequent in younger patients. The recurrence rate was found to be higher in younger patients (RS &amp;gt;16) who refused chemotherapy and lower in patients who received hormonal therapy. There was no significant difference for metastasis in the groups who received chemotherapy or not. All of the older patients with higher RS who refused chemotherapy did not develop a local recurrence or metastasis. Age &amp;lt;50 and Recurrence rate based on cutoff for chemotherapyLow cutoff (RS&amp;lt;16) (p=0.009)High cutoff (RS&amp;gt; 16) (p=0.041)Chemotherapy RecurrenceNo recurrenceTotalRecurrenceNo RecurrenceTotalReceived 2 (50%)2 (50%)42 (6%)31 (94%)33Not received2 (5%)38 (95%)401 (4%)26 (96%)27Refused 0 (0%)2 (100%)22 (33%)4 (67%)6Total4 (9%)42 (91%)465 (8%)61 (92%)66Age &amp;gt;50 and Recurrence based on cutoff for chemotherapyLow cutoff (RS&amp;lt;25) (p=0.019)High cutoff (RS&amp;gt; 25) (p=0.256)Chemotherapy RecurrenceNo recurrenceTotalRecurrenceNo RecurrenceTotalReceived 2 (5%)36 (95%)382 (3%)55 (97%)57Not received 9 (3%)342 (97%)3511 (6%)15 (94%)16Refused 2 (17%)10 (83%)120 (0%)11 (100%)11Total1338840138184Age &amp;lt; 50 and Metastasis based on cutoff for chemotherapyLow cutoff (RS&amp;lt;16) (p=0.111)High cutoff (RS&amp;gt; 16) (p=0.605)Chemotherapy MetastasisNo metastasisTotalMetastasisNo MetastasisTotalReceived 1 (25%)3 (75%)42 (6%)29 (94%)31Not received 1 (3%)38 (97%)393 (11%)24 (89%)27Refused 0 (0%)2 (100%)20 (0%)6 (100%)6Total2434555964Age &amp;gt; 50 and Metastasis based on cutoff for chemotherapyLow cutoff (RS&amp;lt;25) (p=0.111)High cutoff (RS&amp;gt; 25) (p=0.118)Chemotherapy MetastasisNo metastasisTotalMetastasisNo metastasisTotalReceived 1 (3%)37 (97%)383 (5%)53 (95%)56Not received 4 (1%)344 (99%)3481 (6%)15 (94%)16Refused 1 (8%)11 (92%)120 (0%)11 (100%)11Total639239847983 Citation Format: Akisha Glasgow, Philip Bomiesl, Paula Silverman, Hannah Gilmore, Aparna Harbhajanka. Reassessment of traditional oncotype scoring using TAILORx criteria: A large institutional review [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-35.

The prognostic significance of microsatellites in cutaneous melanoma.

Microscopic satellite metastases are an adverse prognostic feature in primary cutaneous melanoma patients. The prognostic significance of microsatellites, including their number, size and distance from the primary melanoma, using the 8th edition American Joint Committee on Cancer definition, has not previously been evaluated. This study sought to determine the prognostic significance of microsatellites in histopathologically reviewed cases. Eighty-seven cases of primary cutaneous melanoma with the presence of microsatellites documented in the original pathology report and all histopathology slides available were reviewed and the findings were correlated with clinical outcome. Matched control cases were selected for all confirmed microsatellites cases. The presence of microsatellites was confirmed in 69 cases. The microsatellite group had significantly worse prognosis, with 21% 5-year disease-free survival compared with 56% in the control group (p < 0.001). The 5-year melanoma-specific survival was 53% in the microsatellites group and 73% in the control group (p = 0.004). Increasing distance (mm) of the microsatellite from the primary melanoma was found to adversely influence disease-free survival (HR = 1.24, 95% CI: 1.13-1.36, p < 0.001), overall survival (HR = 1.26 95%CI: 1.13-1.40, p < 0.001), and melanoma-specific survival (HR = 1.27 95% CI: 1.11-1.45, p < 0.001). Number and size of microsatellites were not significant prognostic factors. The presence of microsatellites was the only factor that proved to be an independent predictor of sentinel node positivity in multivariate analysis (OR 4.64; 95% CI 1.66-12.95; p = 0.003). Microsatellites were significantly associated with more loco-regional recurrences (p < 0.001) but not distant metastases (p = 0.821). Melanomas with microsatellites as defined by the 8th edition American Joint Committee on Cancer staging system are thus aggressive tumors, associated with significantly worse disease-free survival, overall survival and melanoma-specific survival. The presence of microsatellites is also associated with sentinel node-positivity and local and in-transit recurrence. Increasing distance of the microsatellite from the primary tumor is an independent adverse prognostic factor that warrants further evaluation.

Impact of Referral Center Pathology Review on Diagnosis and Management of Patients With Appendiceal Neoplasms.

Data regarding the clinical impact of subspecialist pathology review of appendiceal neoplasms are limited. To determine whether pathology review by gastrointestinal pathologists at a tertiary-care referral center resulted in significant changes in the diagnosis and clinical management of appendiceal neoplastic lesions. We conducted a retrospective review of all patients with an initial diagnosis of appendiceal neoplasm referred to a tertiary-care referral center in Ontario, Canada, from 2010-2016. The discordance rate between original and review pathology reports, the nature of discordances, and the impact of any discordance on patient management were recorded. A total of 145 patients with appendiceal lesions were identified (low-grade mucinous appendiceal neoplasm [n = 79], invasive mucinous adenocarcinoma [n = 12], "colorectal type" adenocarcinoma [n = 12], goblet cell carcinoid and adenocarcinomas ex goblet cell carcinoid [n = 24], and other lesions/neoplasms [n = 20]). One or more changes in diagnoses were found in 36 of 145 cases (24.8%), with changes within the same category of interpretation (n = 10), stage (n = 7), grade (n = 6), and categoric interpretation (n = 5) being the most common. In 10 of 36 patients (28%), the diagnostic change led to a significant change in management, including recommendation for additional surveillance, systemic chemotherapy, additional surgery, or discontinuation of surveillance. Subspecialist pathology review of appendiceal neoplastic lesions led to a change in diagnosis in 36 of 145 cases (24.8%), of which nearly 30% (10 of 36 cases) led to a change in clinical management. The overall rate of clinically significant discordances was 7% (10 of 145). Our findings suggest that subspecialist pathology review of appendiceal neoplasms referred to specialized centers is justified.

179PD - Tumor size and overall survival in a cohort of young (≤40 years), nodenegative, systemically untreated breast cancer patients; by the PARADIGM study group

BackgroundIn the 1990s, the use of adjuvant systemic therapy was based on nodal involvement but not on tumor size, as was recommended in the Dutch breast cancer guidelines. Tumor size is an important prognostic variable in breast cancer, although this may not hold true for all molecular subtypes or patient ages. Here, we studied the prognostic value of tumor size for young (≤40 years at diagnosis), systemically untreated, node-negative (N0), breast cancer patients, and assessed whether for any given T-stage survival exceeds 90% at 20 years. MethodsAll female, breast cancer patients, ≤40 years at time of diagnosis (between 1989 and 2000), were selected from the Netherlands Cancer Registry. All lymph node-positive and systemically treated patients were excluded, resulting in a cohort of 2302 women. Clinico-pathological and follow-up data were collected from national databases, patient records, and the original pathology reports. Multivariate cox regression for overall survival was performed using T-stage (TNM 8.0), molecular subtype, and tumor grade (according to Nottingham Histologic Score) as covariates. ResultsSurvival rates at 20-years are shown in Table. Median follow-up was 17 years. Only 1% had a T3 tumor and these patients were excluded from analysis. The 20-yr OS for the 96 (4%) T1a tumors was 81% (not shown). Women with T2 tumors had a significantly lower OS compared to women with T1a (HR 1.9 P=0.024), T1b (HR 1.7 P=> 0.001) and T1c tumors (HR 1.31 P=0.002), adjusted for tumor grade and molecular subtype. No OS data is shown for subgroups with less than 35 patients.Table179PD Overall survival (OS; %) at 20 years by T-stage, molecular subtype and tumor grade (Gr)TableT1bT1cT2AllnOSnOSnOSnOS3597311146961160230268ER+HER2-Gr 1+2Gr 317282464771655697373436813055834926954All79725569ER-HER2-Gr 1+2Gr 36-31-27-706531-205731586641768All61716368HER2+Gr 1+2Gr 331-745436541595722-8153546116956All70545758 ConclusionsT-stage is associated with OS in this patient group. At 20 years follow-up, we found no T-stage with OS rates >90% in N0, systemically untreated patients, meaning that patients regardless of T-stage may benefit from some form of systemic treatment. Legal entity responsible for the studyThe PARADIGM study group. FundingThe Netherlands Organization for Health Research and Development (ZonMW); A Sister’s Hope; De Vrienden van UMC Utrecht. DisclosureS.C. Linn: Research grant / Funding (self): Amgen; Research grant / Funding (self), unrestricted research grant SUBITO study (NCT02810743): Eurocept-pharmaceuticals; Research grant / Funding (institution), research grant NCT02810743 & olaparib;fulvestrant NCT00738777;advisory board olaparib breast cancer: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution), unrestricted research grant for NCT02285179 and study drug (taselisib): Genentech; Advisory / Consultancy, Member of the Scientific Advisory Board of Cergentis (unpaid): Cergentis; Advisory / Consultancy, scientific advisory board for Watson for Oncology (paid to institution): IBM; Research grant / Funding (institution), unrestricted research grant and study drug NCT03283384; research support biomarker study NCT02109913: Novartis; Advisory / Consultancy, Research grant / Funding (institution), scientific advisory board palbociclib; TEAM 2b through unrestricted research grant from Pfizer: Pfizer; Research grant / Funding (institution), Unrestricted research grant paid to institution for ABC study and study drug: Tesaro; Honoraria (institution), Fee for teaching paid to institution: Bayer. All other authors have declared no conflicts of interest.

Variability in pathologic interpretation of mandibular invasion.

Our objective was to identify the accuracy, sensitivity, and specificity of pathological interpretation of mandibular invasion by oral cavity squamous cell carcinoma (SCC) and compare the sensitivity of detecting mandibular invasion in the erosive versus the infiltrative patterns of invasion. We also aimed to describe the significance of the terminology the carcinoma "abuts the mandible" in pathologic interpretation of mandibular invasion. Retrospective case series. Mandibulectomy specimens from patients who underwent surgical treatment for oral cavity SCC between January 1, 2005 and December 31, 2015 were retrospectively reviewed by a board-certified anatomic pathologist. The accuracy of pathologic interpretation of mandibular invasion was calculated using the retrospective interpretation of bone invasion as the true interpretation, which was compared to the interpretation on the original pathology report. Incidence of encountering the terminology the carcinoma "abuts the mandible" in the pathology report was calculated. A series of 108 consecutive mandibulectomy specimens were reviewed. Sixty-nine percent (74/108) of cases were interpreted as having mandibular invasion. The accuracy of interpreting mandibular invasion was 84%. The sensitivities for interpretation of mandibular invasion for the erosive and infiltrative patterns of invasion were 77% (30/39) and 91% (32/35), respectively (P = .08). Nine percent (10/108) of pathology reports utilized the terminology the carcinoma "abuts the mandible," and 80% (8/10) of these cases exhibited mandibular invasion. The accuracy of identifying mandibular invasion is 84%, indicating a certain degree of sampling error and variability in interpretation. A precise pathologic definition of mandibular invasion should be applied during the interpretation of these specimens to minimize variability. 4 Laryngoscope, 130:1721-1724, 2020.

Comparison of surgical margins for lentigo maligna versus melanoma in situ

Multiple studies have shown a 5-mm surgical margin to be inadequate for excision of melanoma in situ. Some have suggested that a wider margin is needed only for the lentigo maligna subtype. To compare subclinical extension of lentigo maligna with that of melanoma in situ. The secondary objective was to investigate the effect of other factors on extent of subclinical extension. A prospectively collected series of noninvasive melanomas was studied. Original pathology reports were used to identify lentigo maligna and compare data for that subtype with data for the remaining melanomas in situ. A total of 1506 lentigo maligna cases and 829 melanomas in situ were included. To obtain a 97% clearance rate, both lentigo maligna and melanoma in situ required a 12-mm margin on the head and neck and a 9-mm margin on the trunk and extremities. Only 79% of lentigo maligna and 83% of melanoma in situ were successfully excised with a 6-mm margin (P=.12). Local recurrence was identified in 0.26% (5 facial, 1 scalp, and 1 acral), with a mean follow-up time of 5.7years. Margins less than 6mm were not studied. The use of lentigo maligna diagnosis was not used by all dermatopathologists consistently. The degree of surrounding photodamage was not assessed. Subclinical extension of lentigo maligna and melanoma in situ are similar. Standard surgical excision of all melanoma in situ subtypes, including lentigo maligna, should include at least 9mm of normal-appearing skin, which is similar to the amount recommended for early invasive melanoma. Lesions on the head and neck or those with a diameter greater than 1cm may require even wider margins and are best treated with Mohs micrographic surgery. The perception that lentigo maligna has wider subclinical extension may be related to its frequent location on the head and neck, where photodamage can camouflage the clinical border.

Abstract P2-07-04: Prognostic value of residual cancer burden (RCB), neo-bioscore and neoadjuvant response index (NRI) to evaluate response to neoadjuvant trastuzumab-based therapy in HER2-positive breast cancer (BC)

Abstract Intro Pathological complete response (pCR) to neoadjuvant systemic therapy is associated with favorable long-term outcome. As pCR is not an optimal surrogate marker for outcome, other tools were developed to predict long-term outcome more accurately, including the RCB4, NRI3, and Neo-Bioscore5. We evaluated the prognostic value of these tools in a cohort of patients with HER2+ BC with the aim of selecting a group of patients with residual disease but a similar long-term outcome as patients achieving pCR. Methods We included all patients with stage II-III HER2+ BC who were treated with trastuzumab-based neoadjuvant therapy and surgery in the Netherlands Cancer Institute between November 2004 and December 2016. Patients were identified from the institutes' tumor registry and data was collected from the patients' records. To assess RCB scores surgical specimens (breast and axilla tissue) of patients without pCR were retrospectively reviewed. NRI and Neo-Bioscore were calculated based on original pathology reports. Primary endpoint was recurrence-free interval (RFI), defined as time since diagnosis of BC till locoregional or distant recurrence or death from BC, whatever came first. Cox proportional models were used with transformations of RCB, NRI, and Neo-Bioscore. In addition, we evaluated at which cut-off point the NRI could select patients with a similar good prognosis as patients who achieved a pCR, defined by the same lower bound of the 95%CI of the 5-year RFI estimate for the pCR-group. Results 283 women were included, 149 (53%) with HER2+/ER+ BC. 28% received dual HER2-blockade. Median follow-up was 66 months (range 11-148). 157 patients (55%) achieved a pCR in breast and axilla; predicted 5-year RFI for this group was 91% (95%CI 86-96), HR no-pCR vs pCR 2.19, 95%CI 1.07-4.47. Table 1 shows the predicted 5-year RFI and HR for RCB classes. The HR of an RFI event increases gradually for lower NRI values compared to NRI of 1 and gets more steep near NRI values of 0. Patients with a NRI of ≥0.80-0.99 have a 5-year RFI estimate of 90% (95%CI 86-96), HR 1.1 (95%CI 0.6-1.9) compared to patients with NRI of 1 (which is pCR). Table 2 shows the predicted 5-year RFI and HR for the Neo-Bioscore. Table 1RCB classes, estimated 5-year RFI and HRRCBn% 5-year RFI95% CIHR95% CI016392.688.397.111113990.385.295.61.330.672.6526278.469.488.53.181.427.1131135.316.476.113.605.3034.81 Table 2Neo-Bioscore classes, predicted 5-year RFI and HRNeo-Bioscoren% 5-year RFI95% CIHR95% CI01998.795.510011115392.486.099.36.100.9240.5229384.977.493.012.670.76210.4037289.983.896.58.200.62108.2041974.962.989.222.331.76283.445329.410.384.095.206.271446.64610.601.00406.2619.558442.21 Conclusions We show that in a HER2+ BC cohort the RCB and NRI are able to identify a subgroup of patients with limited residual disease after neoadjuvant therapy with similar good prognosis as patients with pCR and therefore may not benefit from additional adjuvant therapy. References 1 Cortazar Lancet 2014 2 FDA Regist 2014 3 Rodenhuis Ann Oncol 2010 4 Symmans JCO 2007 5 Jeruss JCO 2008 6 Mittendorf JAMA Oncol 2016 Citation Format: Steenbruggen TG, van Seijen M, Janssen LM, van Ramshorst MS, van Werkhoven E, Lips EH, Vrancken-Peeters M-JT, Horlings HM, Wesseling J, Sonke GS. Prognostic value of residual cancer burden (RCB), neo-bioscore and neoadjuvant response index (NRI) to evaluate response to neoadjuvant trastuzumab-based therapy in HER2-positive breast cancer (BC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-07-04.

Incidental nonneoplastic parenchymal findings in patients undergoing lung resection for mass lesions

The prevalence of incidental nonneoplastic lung disease in patients undergoing resection for mass lesions is unknown. We determined the prevalence and characteristics of parenchymal findings in patients with lung nodules, aiming to increase awareness of findings that could potentially impact patient management. A total of 397 patients with benign or malignant mass lesions with available presurgical chest computed tomography scans resected between January 2001 and July 2015 were included. Retrospective histologic assessment of parenchymal abnormalities in at least 1 section of grossly normal lung was performed for each case by 2 pulmonary pathologists and correlated with original pathology reports, clinical history, and radiologic findings. A total of 233 women and 164 men underwent resections for carcinomas (78%) or benign nodules (22%). One hundred one (25%) patients showed parenchymal abnormalities, including 14 patients with multiple findings. The most common abnormal findings were fibrotic interstitial changes (10%), including usual interstitial pneumonia (1%), followed by granulomatous processes (8%). Other findings included aspiration (4%), intravascular thrombi (2%), Langerhans cell histiocytosis (1.5%), constrictive bronchiolitis (1%), atypical lymphoid infiltrates (1%), and amyloidosis (0.5%). Abnormalities were more likely to have been documented in the original pathology report by pulmonary pathologists (68%) than by general pathologists (15%) (P < .0001). Cases with histologic parenchymal abnormalities were more likely to show radiologic interstitial lung abnormalities than those without (16% versus 5%; P = .001). Evaluation of background lung parenchyma may yield valuable and unanticipated information in patients undergoing surgical resections for lung masses that may correlate with radiographic interstitial lung abnormalities and influence clinical management.

A Look at Lymphoid Neoplasms in Patients over 65: Are We Less Aggressive - and Does It Affect Outcome?

BACKGROUNDWith a greater proportion of the general population continuing to age from advancements in scientific knowledge, more patients newly diagnosed with malignant lymphoid tumors are elderly (age > 70). Geriatric oncology continues to face challenges in the management of these conditions because of co-morbid conditions, and therapy tolerance limitations associated with aging. Research has shown that geriatric patients get less chemotherapy than non-geriatric counterparts. The main objective of this study was to analyze outcomes of elderly patients (age>65) diagnosed with Hodgkin and Non Hodgkin lymphoma and the relation to several variables including HIV status, financial status and ethnicity.METHODSWe identified and included elderly patients (age >65) diagnosed with any subtype lymphoma by using ICD-9 and ICD-10 codes. The patients identified received care exclusively with Mays Cancer Center at UT Health San Antonio between 1998-2017. Variables for each patient measured included age, gender, diagnosis, stage, > 2 comorbidities, vitality status, HIV status, insurance status, treatment received, and treatment response. Dates of treatment and type of treatment was confirmed by documentation or chemotherapy orders, and diagnosis was confirmed by original pathology report. The statistical significance of associations with treatment response was assessed with Pearson's Chi-Square, Fisher's Exact test, and a logistic regression model with a generalized logit link with a 3-level response (CR, PR, F) where CR was designated as the referent. For each effect, the Odds Ratio (OR) and its 95% confidence interval (95% CI) are reported. All statistical testing was two-sided with a significance level of 5%. SAS Version 9.4 for Windows (SAS Institute, Cary NC) was used throughout.RESULTSOur patient population (n=346) was shown to have a median of 56, female patients (n=174, 50.3%), males patients (n=172, 49.7%), Hispanics (n=180, 52%), uninsured (n=107, 30.9%), and HIV (n=22, 6%). Diagnoses studied included aggressive lymphomas (Burkitt's, 1ry CNS, Hodgkin's, NHL, PTLD; n=252) and indolent lymphomas (Marginal Zone, Follicular; n=94). The odds of treatment failure (F) and of Partial Response (PR) in patients >65 was significantly increased relative to the odds in those ≤65 (F OR=1.04, 95% CI 1.01 to 1.07, p=0.02, PR OR=1.03, 95% CI 1 to 1.05, p=0.032). In an examination of variation in the relation between treatment response and treatment (chemo, chemo/immunotherapy, immune therapy alone, others) with age, we found no overall association between treatment response and treatment after adjustment for age (p=0.92) and no association between treatment response and treatment among those ≤65 or >65 (p=0.54 and p=0.97) respectively.CONCLUSIONHematologic malignancies are potentially curable or may have long lasting remission with current available treatment options; however, age with concurrent declining functional status can preclude many therapies. In our patient population, age did not preclude aggressive treatment with intent for cure. DisclosuresNo relevant conflicts of interest to declare.

Comparison between digital image analysis and visual assessment of immunohistochemical HER2 expression in breast cancer

BackgroundAssessment of HER2 status is considered standard of care in the histopathologic workup of breast cancer and conveys prognostic and predictive information used to guide treatment decisions. The assessment is often carried out in a two-step approach where immunohistochemical expression of HER2 protein is first evaluated by conventional microscopy and equivocal cases are further analyzed by in-situ hybridization techniques to assess gene amplification status. In this study we compared conventional manual assessment of immunohistochemical HER2 expression with digital image analysis (DIA) and consensus manual assessment by a panel of three pathologists. MethodsFrom our archive we retrieved sections of 109 invasive breast carcinomas stained for HER2 with corresponding HER2 score from the original pathology report. The glass slides were assessed by three pathologists to reach a consensus score. Next, the slides were scanned into whole slide images and DIA was performed using Aperio Imagescope. The scoring results were then compared with gene amplification status evaluated by dual in-situ hybridization (DISH). ResultsComparing manual assessment with consensus assessment and DIA, good agreement was obtained with weighted kappa coefficients of 0.79 (manual vs. consensus) and 0.67 (manual vs. DIA). When compared with gene status assessment by DISH, agreement analysis yielded weighted kappa coefficients of 0.52 (manual vs. DISH), 0.58 (consensus vs. DISH) and 0.78 (DIA vs. DISH). There were no false negatives by any of the three methods and false positives ranging from 0.9 to 2.8%. The proportion of equivocal cases by each method was 44% (manual), 33.3% (consensus) and 14.7% (DIA). Application of DIA reduced the number of equivocal cases by 67% without increasing the proportion of false negatives. ConclusionWe conclude that DIA is an accurate method to reduce the number of HER2 equivocal cases without affecting the sensitivity of the HER2 assessment.

Inter-pathologist and pathology report agreement for ovarian tumor characteristics in the Nurses' Health Studies

BackgroundGrade and histotype of ovarian carcinomas are often used as surrogates of molecular subtypes. We examined factors affecting pathologists' reproducibility in two prospective studies. MethodsTwo pathologists independently reviewed slides from 459 incident ovarian cancers in the Nurses' Health Study (NHS) and NHSII. We described agreement on tumor characteristics using percent agreement and Cohen's standard kappa (κ) coefficients. We used logistic regression, with disagreement as the outcome, to evaluate the contribution of case and tumor characteristics to agreement. ResultsInter-rater agreement was 95% (κ = 0.81) for carcinoma versus borderline, 89% (κ = 0.58) for grade and 85% (κ = 0.71) for histotype. Inter-rater grading disagreement was higher for non-serous histotypes (OR = 4.66, 95% CI 2.09–10.36) and lower for cancers with bizarre atypia (OR = 0.13, 95% CI 0.04–0.38). Agreement with original pathology reports was 94% (κ = 0.73) for carcinoma versus borderline, 78% (κ = 0.60) for histotype, and 79% (κ = 0.24) for grade. Grading disagreement was significantly lower for tumors with ‘solid, pseudoendometrioid or transitional’ (SET) architecture (OR = 0.08, 95%CI 0.01–0.84). Date of original diagnosis, hospital type, number of slides available for review, tumor stage, and slide quality were not related to agreement. ConclusionOverall, inter-rater agreement for tumor type and grade for archival tissue specimens was good. Agreement between the consensus review and original pathology reports was lower. Factors contributing to grading disagreement included non-serous histotype, absence of bizarre atypia, and absence of SET architecture.

False-positive findings on 6-[18F]fluor-l-3,4-dihydroxyphenylalanine PET (18F-FDOPA-PET) performed for imaging of neuroendocrine tumors.

PET with 6-[18F]fluor-l-3,4-dihydroxyphenylalanine (18F-FDOPA) has been shown to be a useful imaging tool with a high sensitivity for the visualization of neuroendocrine tumors (NETs). 18F-FDOPA uptake in tumors other than NETs has been suggested previously, but data on this phenomenon are limited. We therefore studied the non-physiological, false-positive uptake of 18F-FDOPA in a large population of patients with a NET or with a high clinical suspicion of harboring a NET. Retrospective single-center study among adult patients in whom 18F-FDOPA PET scintigraphy was performed between January 2004 and December 2014. The original scan report was compared with the original pathology report corresponding with the 18F-FDOPA PET-positive lesion. In case this was inconsistent with the diagnosis of a NET, both the scan and the pathology slides were reassessed. Specimens of these non-NET tissues were immunohistochemically stained for AADC. 1070 18F-FDOPA PET scans from 705 patients were evaluated. Focal or multiple 18F-FDOPA-avid lesions were described in 709 18F-FDOPA PET scans (66%). Histology of these 18F-FDOPA PET-positive lesions was present in 508 (72%) cases. In seven cases, the histopathology was not compatible with NET but showed squamous cell carcinoma of the cervix, multiple myeloma (two cases), hepatocellular carcinoma, Schwannoma, adrenocortical carcinoma and a skeletal myxoid chondrosarcoma, with positive immunohistochemical staining for AADC in 67%. Pathological uptake of 18F-FDOPA does not always indicate the presence of a NET. The possibility of 18F-FDOPA uptake by tumor types other than NETs, although rare, should be considered.