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Article: Using an anomaly detection approach for the segmentation of colorectal cancer tumors in whole slide images.

Gu, Qiangqiang / Meroueh, Chady / Levernier, Jacob / Kroneman, Trynda / Flotte, Thomas / Hart, Steven

2023 Volume 14, Page(s) 100336

Abstract: Colorectal cancer (CRC) is the second most commonly diagnosed cancer in the United States. Genetic testing is critical in assisting in the early detection of CRC and selection of individualized treatment plans, which have shown to improve the survival ... ...

Abstract	Colorectal cancer (CRC) is the second most commonly diagnosed cancer in the United States. Genetic testing is critical in assisting in the early detection of CRC and selection of individualized treatment plans, which have shown to improve the survival rate of CRC patients. The tissue slide review (TSR), a tumor tissue macro-dissection procedure, is a required pre-analytical step to perform genetic testing. Due to the subjective nature of the process, major discrepancies in CRC diagnostics by pathologists are reported, and metrics for quality are often only qualitative. Progressive context encoder anomaly detection (P-CEAD) is an anomaly detection approach to detect tumor tissue from whole slide images (WSIs), since tumor tissue is by its nature, an anomaly. P-CEAD-based CRC tumor segmentation achieves a 71% 26% sensitivity, 92% 7% specificity, and 63% 23% F1 score. The proposed approach provides an automated CRC tumor segmentation pipeline with a quantitatively reproducible quality compared with the conventional manual tumor segmentation procedure.
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2579241-6
ISSN	2153-3539 ; 2229-5089
ISSN (online)	2153-3539
ISSN	2229-5089
DOI	10.1016/j.jpi.2023.100336
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Article ; Online: Sinonasal Mucosal Melanoma: Role of Tumor Proliferative Indices and Pathological Factors in Survival.

Guo, Ruifeng / Jenkins, Sarah M / Johnson, Brian J / Reed, Katelyn / Kroneman, Trynda / Choby, Garret

The Laryngoscope

2022 Volume 132, Issue 12, Page(s) 2350–2358

Abstract: Objective: The objective of this study is to determine the association of proliferation indices and pathologic biomarkers on overall and recurrence/metastasis-free survival (OS and RMFS) in patients with sinonasal mucosal melanoma (SNMM) and to assess ... ...

Abstract	Objective: The objective of this study is to determine the association of proliferation indices and pathologic biomarkers on overall and recurrence/metastasis-free survival (OS and RMFS) in patients with sinonasal mucosal melanoma (SNMM) and to assess the genetic mutational landscape of SNMM. Methods: This is a retrospective cohort study of 45 SNMM patients without neoadjuvant therapy who underwent surgical therapy with curative intent and had tumor tissue available for histopathologic review, molecular analysis, and genetic mutational assessment. The OS and RMFS were assessed for associations with numerous tumor and patient-related factors. Results: Among proliferative indices, higher Ki67 and mitotic rates were associated with worsened OS and RMFS (Ki67: p = 0.0007 and p < 0.0001; mitotic rate: p = 0.005 and p = 0.0009, respectively). The presence of brisk tumor-infiltrating lymphocytes (TILs) was associated with improved RMFS (p = 0.007) and the presence of lymphovascular invasion was associated with worsened OS and RMFS (p = 0.02 and p = 0.04, respectively). Patients with amelanotic tumors were more likely to have higher T-stage (p = 0.046), less likely to have brisk TILs (p = 0.02) and had worsened RMFS (p = 0.03). Patients on immunotherapy with tumor Ki67 < 40% had better 3-year OS compared to those with higher Ki67 index (p = 0.004). Actionable genetic mutations such as BRAF V600E are rare and present in only 1 of 20 patients tested. Conclusion: In SNMM patients, pathologic and proliferation markers such as Ki67, mitotic rate and brisk TILs are associated with survival and may be considered in future staging systems. Clinical response to immunotherapy appears to correlate with the Ki67 index. Given the distinct genetic profile of SNMM, targeted therapies against the MAPK kinase pathway have limited utility. Level of evidence: 3 Laryngoscope, 132:2350-2358, 2022.
MeSH term(s)	Humans ; Ki-67 Antigen ; Retrospective Studies ; Paranasal Sinus Neoplasms/genetics ; Paranasal Sinus Neoplasms/surgery ; Paranasal Sinus Neoplasms/pathology ; Melanoma/pathology ; Lymphocytes, Tumor-Infiltrating/pathology ; Prognosis
Chemical Substances	Ki-67 Antigen
Language	English
Publishing date	2022-06-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	80180-x
ISSN	1531-4995 ; 0023-852X
ISSN (online)	1531-4995
ISSN	0023-852X
DOI	10.1002/lary.30240
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Article ; Online: Democratizing Artificial Intelligence in Anatomic Pathology.

Flotte, Thomas J / Derauf, Stephanie A / Byrd, Rachel K / Kroneman, Trynda N / Bell, Debra A / Stetzik, Lucas / Lee, Seung-Yi / Samiei, Alireza / Hart, Steven N / Garcia, Joaquin J / Beamer, Gillian / Westerling-Bui, Thomas

Archives of pathology & laboratory medicine

2024

Language	English
Publishing date	2024-04-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2023-0205-OA
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Article ; Online: Phase I trial of adjuvant mature autologous dendritic cell/allogeneic tumor lysate vaccines in combination with temozolomide in newly diagnosed glioblastoma.

Parney, Ian F / Anderson, S Keith / Gustafson, Michael P / Steinmetz, Susan / Peterson, Timothy E / Kroneman, Trynda N / Raghunathan, Aditya / O'Neill, Brian P / Buckner, Jan C / Solseth, Mary / Dietz, Allan B

Neuro-oncology advances

2022 Volume 4, Issue 1, Page(s) vdac089

Abstract: Background: Glioblastoma (GBM) has poor prognosis despite aggressive treatment. Dendritic cell (DC) vaccines are promising, but widespread clinical use has not been achieved, possibly reflecting manufacturing issues of antigen choice and DC potency. We ... ...

Abstract	Background: Glioblastoma (GBM) has poor prognosis despite aggressive treatment. Dendritic cell (DC) vaccines are promising, but widespread clinical use has not been achieved, possibly reflecting manufacturing issues of antigen choice and DC potency. We previously optimized vaccine manufacture utilizing allogeneic human GBM tumor cell lysate and potent, mature autologous DCs. Here, we report a phase I study using this optimized DC vaccine in combination with standard therapy. Methods: Following surgical resection and radiation with concurrent temozolomide (TMZ), newly diagnosed adult GBM patients received intradermal DC vaccines plus TMZ. Primary endpoints were safety and feasibility. Immune and treatment responses were recorded. Results: Twenty-one patients were enrolled in this study. One progressed between leukapheresis and vaccine manufacture. Twenty patients received treatment per protocol. Vaccine doses (≥15) were generated following a single leukapheresis for each patient. No dose-limiting vaccine toxicities were encountered. One patient had symptomatic, histologically proven pseudoprogression. Median progression-free survival was 9.7 months. Median overall survival was 19 months. Overall survival was 25% at 2 years and 10% at 4 years. One patient remains progression-free 5 years after enrollment. Specific CD8 T-cell responses for the tumor-associated antigen gp100 were seen post-vaccination. Patients entered the trial with a leukocyte deficit compared to healthy donors which partly normalized over the course of therapy. Conclusions: This vaccine platform is safe and highly feasible in combination with standard therapy for newly diagnosed patients. Imaging, histological, survival, and immunological data suggest a positive biological response to therapy that warrants further investigation.
Language	English
Publishing date	2022-06-24
Publishing country	England
Document type	Journal Article
ZDB-ID	3009682-0
ISSN	2632-2498 ; 2632-2498
ISSN (online)	2632-2498
ISSN	2632-2498
DOI	10.1093/noajnl/vdac089
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Article ; Online: Ki-67 Labeling Index in Pulmonary Carcinoid Tumors: Comparison Between Small Biopsy and Resection Using Tumor Tracing and Hot Spot Methods.

Boland, Jennifer M / Kroneman, Trynda N / Jenkins, Sarah M / Terra, Simone B S P / Xie, Hao / Molina, Julian / Mounajjed, Taofic / Roden, Anja C

Archives of pathology & laboratory medicine

2020

Abstract: Context.—: Pulmonary carcinoids are classified as typical or atypical by assessing necrosis and mitoses, which usually cannot be adequately assessed on small biopsies. Ki-67 is not currently used to grade pulmonary carcinoids, but it may be helpful to ... ...

Abstract	Context.—: Pulmonary carcinoids are classified as typical or atypical by assessing necrosis and mitoses, which usually cannot be adequately assessed on small biopsies. Ki-67 is not currently used to grade pulmonary carcinoids, but it may be helpful to determine preliminary grade in biopsies. However, the rate at which Ki-67 could underestimate or overestimate grade on small biopsies has not been well studied. Objective.—: To compare Ki-67 labeling obtained on small biopsies to subsequent resection. Design.—: Ki-67 was performed on paired biopsy and resection specimens from 55 patients. Slides were scanned using Aperio ScanScope. Labeling index was determined using automated hot spot and tumor tracing methods. Results.—: The study included 41 typical and 14 atypical carcinoids. Atypical carcinoids were larger and had more distant metastases. Death from disease occurred in 3 patients (all had atypical carcinoids). Median hot spot Ki-67 labeling index was greater in resection compared with biopsy by 0.7% ( Conclusions.—: Hot spot Ki-67 tends to underestimate grade on small biopsies, whereas grade is overestimated by tumor tracing. Hot spot Ki-67 cutoff of 3.5% predicted atypical histology for both biopsy and resection. Different biopsy and resection cutoffs were necessary for tumor tracing, which would make clinical implementation more difficult.
Language	English
Publishing date	2020-01-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2019-0374-OA
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Article ; Online: Ki-67 "hot spot" digital analysis is useful in the distinction of hepatic adenomas and well-differentiated hepatocellular carcinomas.

Jones, Andrea / Kroneman, Trynda N / Blahnik, Anthony J / Graham, Rondell P / Mounajjed, Taofic / Torbenson, Michael S / Moreira, Roger K

Virchows Archiv : an international journal of pathology

2020 Volume 478, Issue 2, Page(s) 201–207

Abstract: This study aims to investigate the utility of digital protocols for Ki-67 immunohistochemistry quantitative analysis ("hot spot" method) in the setting of well-differentiated hepatocellular neoplasms. Resection cases of typical hepatic adenomas (HAs) (n = ...

Abstract	This study aims to investigate the utility of digital protocols for Ki-67 immunohistochemistry quantitative analysis ("hot spot" method) in the setting of well-differentiated hepatocellular neoplasms. Resection cases of typical hepatic adenomas (HAs) (n = 40), atypical HAs (n = 9), and well-differentiated hepatocellular carcinomas (WD HCCs) (n = 56) were selected. HAs were further classified by immunohistochemistry using antibodies against liver fatty acid binding protein, glutamine synthetase, B-catenin, hepatic serum amyloid A, and C-reactive protein. Ki-67 proliferative index by immunohistochemistry was evaluated in all cases by digital analysis using a modified neuroendocrine tumor "hot spot" protocol. The proliferative rate of HAs (typical, median 1.2% (range 0-7.4%) and atypical, median 1.0% (range 0.3-3%)) was significantly lower than that of WD HCCs (median 4.5%, range 0-49.8%) (P < 0.0001). Only a few (7.5%) of the adenomas (all inflammatory/telangiectatic type) had proliferative rates higher than 4%, compared to most (51%) of HCCs. Ki-67 is a potentially useful adjunct marker in the evaluation of WD hepatocellular neoplasms, as "hot spot" proliferative rates are consistently very low in HAs but vary significantly in WD HCCs.
MeSH term(s)	Adenoma/chemistry ; Adenoma/pathology ; Adenoma/surgery ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular/chemistry ; Carcinoma, Hepatocellular/pathology ; Carcinoma, Hepatocellular/surgery ; Cell Differentiation ; Cell Proliferation ; Child ; Diagnosis, Differential ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Immunohistochemistry ; Ki-67 Antigen/analysis ; Liver Neoplasms/chemistry ; Liver Neoplasms/pathology ; Liver Neoplasms/surgery ; Male ; Microscopy ; Middle Aged ; Predictive Value of Tests ; Reproducibility of Results ; Young Adult
Chemical Substances	Ki-67 Antigen ; MKI67 protein, human
Language	English
Publishing date	2020-06-25
Publishing country	Germany
Document type	Comparative Study ; Journal Article
ZDB-ID	1184867-4
ISSN	1432-2307 ; 0945-6317
ISSN (online)	1432-2307
ISSN	0945-6317
DOI	10.1007/s00428-020-02868-8
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Article ; Online: The Influence of Tumor Stage on the Prognostic Value of Ki-67 Index and Mitotic Count in Small Intestinal Neuroendocrine Tumors.

Sun, Yu / Lohse, Christine / Smyrk, Thomas / Hobday, Timothy / Kroneman, Trynda / Zhang, Lizhi

The American journal of surgical pathology

2017 Volume 42, Issue 2, Page(s) 247–255

Abstract: Tumor cell proliferation rate determined by either Ki-67 index or mitotic count (MC) has shown to be a prognostic factor for gastrointestinal neuroendocrine tumors in general, and after its incorporation in the 2010 World Health Organization tumor ... ...

Abstract	Tumor cell proliferation rate determined by either Ki-67 index or mitotic count (MC) has shown to be a prognostic factor for gastrointestinal neuroendocrine tumors in general, and after its incorporation in the 2010 World Health Organization tumor grading system, it has become essentially mandatory in pathology reports for all gastrointestinal neuroendocrine tumors, regardless of tumor location. Nevertheless, clinical significance for the Ki-67 index or MC has not been well demonstrated in small intestinal neuroendocrine tumor (SINET), especially those without distant metastasis, the majority of which have very low proliferation rates. We assessed the clinical behavior of 130 SINETs in relation to stage, Ki-67 index, MC, and other pathologic features. Most SINETs (86%) were grade 1 and 14% were grade 2. There were no grade 3 tumors or poorly differentiated neuroendocrine carcinomas. On multivariate analysis, age, Ki-67 index >5%, MC >10/50 high-power field, stage IV, and liver metastases were associated with increased risk of death in all patients. When both stage and grade were considered, Ki-67 index >5% was associated with a nearly 4-fold increased risk of death in stage IV cases (n=60). In contrast, Ki-67 index did not show prognostic value for patients with stages I to III disease (n=70), although MC >1/50 high-power field was significantly associated with death on multivariable analysis. Our study confirms that liver metastasis and increased tumor cell proliferation rate are independent prognostic factors for SINETs, but shows that most SINETs have a very low proliferation rate, which limits its value for predicting tumor behavior. By combining staging and grading information, we demonstrate different roles and cutoff values of Ki-67 index and MC in SINET with different stages.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Cell Differentiation ; Cell Proliferation ; Female ; Humans ; Ileal Neoplasms/chemistry ; Ileal Neoplasms/mortality ; Ileal Neoplasms/pathology ; Ileal Neoplasms/surgery ; Immunohistochemistry ; Jejunal Neoplasms/chemistry ; Jejunal Neoplasms/mortality ; Jejunal Neoplasms/pathology ; Jejunal Neoplasms/surgery ; Ki-67 Antigen/analysis ; Liver Neoplasms/secondary ; Male ; Middle Aged ; Mitosis ; Mitotic Index ; Neoplasm Grading ; Neoplasm Staging ; Neuroendocrine Tumors/chemistry ; Neuroendocrine Tumors/mortality ; Neuroendocrine Tumors/pathology ; Neuroendocrine Tumors/surgery ; Predictive Value of Tests ; Reproducibility of Results
Chemical Substances	Ki-67 Antigen ; MKI67 protein, human
Language	English
Publishing date	2017-10-06
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Validation Studies
ZDB-ID	752964-8
ISSN	1532-0979 ; 0147-5185
ISSN (online)	1532-0979
ISSN	0147-5185
DOI	10.1097/PAS.0000000000000968
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Article: Increased Plasma Cells and Decreased B-cells in Tumor Infiltrating Lymphocytes are Associated with Worse Survival in Lung Adenocarcinomas.

Lee, Hee Eun / Luo, Lei / Kroneman, Trynda / Passow, Marie R / Del Rosario, Kristina M / Christensen, Michael R / Francis, Mary E / O'Shaughnessy, John W / Blahnik, Anthony J / Yang, Ping / Yi, Eunhee S

Journal of clinical & cellular immunology

2020 Volume 11, Issue 1

Abstract: Introduction: Clinical significance of tumor-infiltrating plasma cells and B-cells in lung adenocarcinoma is not well known.: Methods: CD3, CD20 and MUM1 immunostains were performed on representative tumor blocks selected from 120 consecutive lung ... ...

Abstract	Introduction: Clinical significance of tumor-infiltrating plasma cells and B-cells in lung adenocarcinoma is not well known. Methods: CD3, CD20 and MUM1 immunostains were performed on representative tumor blocks selected from 120 consecutive lung adenocarcinoma cases treated by surgical resection at Mayo Clinic Rochester. CD3 Results: Median age of patients was 69 years (range, 46-91 years) and 52 were male. Median numbers (interquartile range) of CD20 Conclusion: High plasma cell % among TILs in the tumor area and low IE B-cell count were associated with worse prognosis in lung adenocarcinoma patients.
Language	English
Publishing date	2020-01-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2684688-3
ISSN	2155-9899
ISSN	2155-9899
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Article ; Online: Tao brush endometrial cytology is a sensitive diagnostic tool for cancer and hyperplasia among women presenting to clinic with abnormal uterine bleeding.

DeJong, Stephanie R / Bakkum-Gamez, Jamie N / Clayton, Amy C / Henry, Michael R / Keeney, Gary L / Zhang, Jun / Kroneman, Trynda N / Laughlin-Tommaso, Shannon K / Ahlberg, Lisa J / VanOosten, Ann L / Weaver, Amy L / Wentzensen, Nicolas / Kerr, Sarah E

Cancer medicine

2021 Volume 10, Issue 20, Page(s) 7040–7047

Abstract: Background: Abnormal uterine bleeding requires the investigation of the endometrium. Histology is typically used but there remains room for the improvement and use of cytology.: Methods: Women presenting for clinically indicated office endometrial ... ...

Abstract	Background: Abnormal uterine bleeding requires the investigation of the endometrium. Histology is typically used but there remains room for the improvement and use of cytology. Methods: Women presenting for clinically indicated office endometrial biopsy were prospectively enrolled. Tao endometrial brushing and office endometrial biopsy were performed, and surgical procedure if clinically indicated. Tao brush cytology specimens were blindly reviewed by up to three pathologists, consensus obtained, and scored as: benign, atypical (favor benign), suspicious, positive for malignancy, or non-diagnostic. Cytology and histology were compared to surgical pathology to determine sensitivity, specificity, positive, and negative predictive values to detect AH (atypical hyperplasia) or EC (endometrial cancer). Results: Clinical indications of 197 enrolled patients included postmenopausal bleeding (90, 45.7%), abnormal uterine bleeding (94, 47.7%), and abnormal endometrium on ultrasound without bleeding (13, 6.6%). Of the 197 patients, 185 (93.9%) had cytology score consensus and a total of 196 (99.5%) had consensus regarding cytology positivity. Surgical pathology diagnoses (N = 85) were 13 (15.3%) FIGO grade 1 or 2 EC, 3 (3.5%) AH, and 69 (81.2%) benign endometrium. Sensitivity and specificity to detect EC or AH were 93.7% and 100%, respectively, via endometrial biopsy; 87.5% and 63.8%, respectively, via endometrial cytology when scores of malignancy, suspicious, or atypical were considered positive. Conclusions: In a high-risk population, Tao brush endometrial cytology showed high sensitivity to detect AH and EC comparable to biopsy histology when considering scores of malignancy, suspicious, atypical, and non-diagnostic. Revisiting the potential value of endometrial cytology in the contemporary era of endometrial diagnostic workup is warranted.
MeSH term(s)	Aged ; Biopsy/instrumentation ; Biopsy/methods ; Cytodiagnosis/instrumentation ; Cytodiagnosis/methods ; Endometrial Neoplasms/complications ; Endometrial Neoplasms/pathology ; Endometrium/diagnostic imaging ; Endometrium/pathology ; Female ; Humans ; Hyperplasia/pathology ; Middle Aged ; Postmenopause ; Predictive Value of Tests ; Prospective Studies ; Sensitivity and Specificity ; Ultrasonography ; Uterine Hemorrhage/etiology
Language	English
Publishing date	2021-09-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.4235
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Article: Macrophage Density Predicts Facial Nerve Outcome and Tumor Growth after Subtotal Resection of Vestibular Schwannoma.

Graffeo, Christopher S / Perry, Avital / Raghunathan, Aditya / Kroneman, Trynda N / Jentoft, Mark / Driscoll, Colin L / Neff, Brian A / Carlson, Matthew L / Jacob, Jeffrey / Link, Michael J / Van Gompel, Jamie J

Journal of neurological surgery. Part B, Skull base

2018 Volume 79, Issue 5, Page(s) 482–488

Abstract: ... ...

Abstract	Introduction
Language	English
Publishing date	2018-02-07
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2654269-9
ISSN	2193-634X ; 2193-6331
ISSN (online)	2193-634X
ISSN	2193-6331
DOI	10.1055/s-0038-1627474
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