UNASSIGNED: There is a lack of published information outlining the use of biologics in National Football League (NFL) athletes and limited data to guide biologic treatment strategies.
UNASSIGNED: To develop a consensus on the use of biologics among NFL team physicians.
UNASSIGNED: Consensus statement.
UNASSIGNED: A working group of 6 experts convened a consensus process involving NFL team physicians using validated Delphi methodology. Physicians from 32 NFL teams as well as NFL London were invited to take part. This iterative process was used to define statements on the use of biologics in NFL athletes. A recent scoping review exploring biologics in professional athletes was used to inform the first of 3 rounds of surveys, with statements considered under 7 headings: biologics in general, challenges of treating NFL athletes, terminology/nomenclature, autologous blood products, cell-based therapies, guidance for NFL team physicians, and biologic research in the NFL. In addition to rating agreement, experts were encouraged to propose further items or modifications. Predefined criteria were used to refine item lists after each survey. For a consensus within the final round, defined a priori, items were included in the final information set if a minimum of 75% of respondents agreed and fewer than 10% disagreed.
UNASSIGNED: Physicians from 26 NFL teams and NFL London responded to the initial invitation to participate in the Delphi process; 88.9% of participating team physicians completed the round 1 survey, with response rates of 87.5% in round 2 and 95.2% in round 3. After 3 rounds, 47 statements reached a consensus. A consensus was achieved that platelet-rich plasma has a positive impact on patellar tendinopathy and on symptoms in early osteoarthritis but not for other indications. NFL team physicians agreed that while cell therapies have the potential to improve symptoms, the misrepresentation of uncharacterized preparations as \"stem cells\" has contributed to the widespread use of unproven therapies.
UNASSIGNED: This study established an expert consensus on 47 statements relating to the use of biologics in NFL athletes. In addition to providing clinical guidance for the use of biologics in NFL athletes, this study identified key areas for future focus including the development of athlete education materials.

Background. Classification of phyllodes tumors is challenging due unclear diagnostic criteria, recently addressed by consensus review criteria. Herein, we reviewed all malignant phyllodes tumor resections and reclassified them based on the consensus guidelines, correlating with outcome. We hypothesize that application of criteria would result in a significant proportion being \"down-graded\" to either borderline or benign phyllodes tumor. Methods. Primary resections of malignant phyllodes tumor were reviewed by four AP board-certified, breast fellowship-trained pathologists. Morphologic variables delineated in consensus guidelines (ie stromal cellularity, cellular atypia, tumor border, presence of heterologous elements, presence of stromal overgrowth) were evaluated. Following review, cases were reclassified as benign, borderline, or malignant. Results. Upon reclassification, 20% (5/20) cases were \"down-graded\" to borderline phyllodes tumor while 80% (15/20) remained malignant phyllodes tumor. Two morphologic features were statistically significant including broadly infiltrating tumor border in 80% (12/15) of malignant phyllodes tumors compared to none in borderline phyllodes tumor (0/5) (p = 0.004) and stromal overgrowth in 67% (10/15) of malignant phyllodes tumor compared to none in borderline phyllodes tumors (0/5) (p = 0.03). Upon review of the pathology reports, 30% (6/20) contained all 5 histomorphologic variables delineated in the consensus review criteria. Malignant phyllodes tumor resulted in five cases with recurrence (33.3%, 5/15) and three cases with metastases (20.0%, 3/15) and borderline phyllodes tumor resulted in one case with recurrence (20.0%, 1/5) and no metastases (0/5). Conclusion. The consensus guidelines for phyllodes tumor are useful for subclassification. We hypothesize that standardize reporting of the histomorphologic variables may lead to better consensus.

With the major development of immunotherapies, evaluation of the immune response associated to cancer has become the new challenge for pathologists. In breast cancer, this perspective has been notably anticipated by the recent publication, in 2014, of international guidelines for assessment of tumor-infiltrating lymphocytes (TILs), on routine haematoxylin-eosin stains. This technical article aims at reviewing the main key points and different steps in evaluation of tumor-infiltrating lymphocytes, in order to allow an easy implementation of this putative biomarker in routine practice. Widespread diffusion of international guidelines is the key to development of a standardized and reproducible biomarker. This early learning phase is of particular importance, as immune response will probably play a major role as a prognostic and predictive biomarker, especially in triple-negative and HER2 positive breast cancer.

OBJECTIVE: A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled.
METHODS: We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients.
RESULTS: We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed.
CONCLUSIONS: Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and Kopetz, p. 3989.

A combination of karyotyping and aneuploidy analysis by interphase fluorescent in situ hybridization is a sensitive method for evaluation of genetic stability of stem cell cultures. The methodology and specific features of preparing and analyzing the cytogenetic preparations are described as exemplified by human multipotent mesenchymal stromal cells.

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BACKGROUND: The clinical heterogeneity of polycystic ovary syndrome (PCOS) is mirrored by the unceasing debate on the most appropriate diagnostic criteria.
RESULTS: To highlight differences and inconsistencies between NIH and ESHRE/ASRM criteria, we applied them to 375 patients with oligo/amenorrhoea and signs of hyperandrogenism. Among them, we identified 273 women with PCOS according to NIH, whereas up to 345 patients fulfilled ESHRE/ASRM criteria. The 72 patients, constituting the gap between the two classifications, exhibited a lower expression of clinical signs compared with the 273 patients matching both criteria. To the whole group, we then applied the ESHRE/ASRM criteria modified to include an easily reproducible ultrasound examination of the ovarian stroma (UCSC criteria). In this way, we identified 30 women who were healthy according to all criteria, 37 affected by PCOS according only to the ESHRE/ASRM Consensus, 35 affected according only to the UCSC and ESHRE/ASRM criteria and 273 who were considered to have PCOS by all criteria. These groups showed a progressively increasing expression of PCOS features.
CONCLUSIONS: In the grey area between NIH and ESHRE/ASRM classifications, UCSC criteria could identify a subgroup of women, missed by NIH criteria, with more pronounced stigmas than those identified by ESHRE/ASRM criteria alone, and who may profit more from a targeted therapy.

As a result of major recent advances in understanding the biology of gastrointestinal stromal tumors (GISTs), specifically recognition of the central role of activating KIT mutations and associated KIT protein expression in these lesions, and the development of novel and effective therapy for GISTs using the receptor tyrosine kinase inhibitor STI-571, these tumors have become the focus of considerable attention by pathologists, clinicians, and patients. Stromal/mesenchymal tumors of the gastrointestinal tract have long been a source of confusion and controversy with regard to classification, line(s) of differentiation, and prognostication. Characterization of the KIT pathway and its phenotypic implications has helped to resolve some but not all of these issues. Given the now critical role of accurate and reproducible pathologic diagnosis in ensuring appropriate treatment for patients with GIST, the National Institutes of Health convened a GIST workshop in April 2001 with the goal of developing a consensus approach to diagnosis and morphologic prognostication. Key elements of the consensus, as described herein, are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term \"benign\" for any GIST, at least at the present time.

As a result of major recent advances in understanding the biology of gastrointestinal stromal tumors (GIST), specifically recognition of the central role of activating KIT mutations and associated KIT protein expression in these lesions, and the development of novel and effective therapy for GISTs using the receptor tyrosine kinase inhibitor STI-571, these tumors have become the focus of considerable attention among pathologists, clinicians, and patients. Stromal/mesenchymal tumors of the gastrointestinal tract have long been a source of confusion and controversy with regard to classification, line(s) of differentiation, and prognostication. Characterization of the KIT pathway and its phenotypic implications has helped to resolve some but not all of these issues. Given the now critical role of accurate and reproducible pathologic diagnosis in ensuring appropriate treatment for patients with GIST, the National Institutes of Health (NIH) convened a GIST workshop in April 2001 with the goal of developing a consensus approach to diagnosis and morphologic prognostication. Key elements of the consensus, as described herein, are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term benign for any GIST, at least at the present time.

Mesenchymal stem cells (MSCs) are believed to be the common precursors to differentiated cell lineages found in bone and bone marrow, including adipocytes, chondrocytes, osteoblasts, and hematopoiesis-supporting stroma. Apart from this fact, most aspects of MSC biology, including their ontogeny, anatomical location in marrow, and in vivo functions remain vague. Attempts to clarify these issues have produced confounding results, principally due to the fact that many researchers employ different methods to culture MSCs, assess their differentiation potential, and evaluate their capacity for self-renewal. Accordingly, the current status of the field appears fragmentary with no clear consensus on how to define the cells. In describing past and present contributions to the field of MSC research, I will demonstrate that the apparent incongruity of the literature is misleading, and that an unbiased interpretation reveals a fairly cohesive picture of MSC biology.