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The Banff Working Group Classification of Definitive Polyomavirus Nephropathy: Morphologic Definitions and Clinical Correlations.

ABSTRACT: Polyomavirus nephropathy (PVN) is a common viral infection of renal allografts, with biopsy-proven incidence of approximately 5%. A generally accepted morphologic classification of definitive PVN that groups histologic changes, reflects clinical presentation, and facilitates comparative outcome analyses is lacking. Here, we report a morphologic classification scheme for definitive PVN from the Banff Working Group on Polyomavirus Nephropathy, comprising nine transplant centers in the United States and Europe. This study represents the largest systematic analysis of definitive PVN undertaken thus far. In a retrospective fashion, clinical data were collected from 192 patients and correlated with morphologic findings from index biopsies at the time of initial PVN diagnosis. Histologic features were centrally scored according to Banff guidelines, including additional semiquantitative histologic assessment of intrarenal polyomavirus replication/load levels. In-depth statistical analyses, including mixed effects repeated measures models and logistic regression, revealed two independent histologic variables to be most significantly associated with clinical presentation: intrarenal polyomavirus load levels and Banff interstitial fibrosis ci scores. These two statistically determined histologic variables formed the basis for the definition of three PVN classes that correlated strongest with three clinical parameters: presentation at time of index biopsy, serum creatinine levels/renal function over 24 months of follow-up, and graft failure. The PVN classes 1-3 as described here can easily be recognized in routine renal biopsy specimens. We recommend using this morphologic PVN classification scheme for diagnostic communication, especially at the time of index diagnosis, and in scientific studies to improve comparative data analysis.

SUBMITTER: Nickeleit V

PROVIDER: S-EPMC5791071 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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The Banff Working Group Classification of Definitive Polyomavirus Nephropathy: Morphologic Definitions and Clinical Correlations.

Nickeleit Volker V Singh Harsharan K HK Randhawa Parmjeet P Drachenberg Cinthia B CB Bhatnagar Ramneesh R Bracamonte Erika E Chang Anthony A Chon W James WJ Dadhania Darshana D Davis Vicki G VG Hopfer Helmut H Mihatsch Michael J MJ Papadimitriou John C JC Schaub Stefan S Stokes Michael B MB Tungekar Mohammad F MF Seshan Surya V SV

Journal of the American Society of Nephrology : JASN 20171226 2

Polyomavirus nephropathy (PVN) is a common viral infection of renal allografts, with biopsy-proven incidence of approximately 5%. A generally accepted morphologic classification of definitive PVN that groups histologic changes, reflects clinical presentation, and facilitates comparative outcome analyses is lacking. Here, we report a morphologic classification scheme for definitive PVN from the Banff Working Group on Polyomavirus Nephropathy, comprising nine transplant centers in the United State ...[more]

PMID: 29279304

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Project description:BackgroundIn melanoma, morphology-based classification systems have not been able to provide relevant information for selecting treatments for patients whose tumors have metastasized. The recent identification of causative genetic alterations has revealed mutations in signaling pathways that offer targets for therapy. Identifying morphologic surrogates that can identify patients whose tumors express such alterations (or functionally equivalent alterations) would be clinically useful for therapy stratification and for retrospective analysis of clinical trial data.Methodology/principal findingsWe defined and assessed a panel of histomorphologic measures and correlated them with the mutation status of the oncogenes BRAF and NRAS in a cohort of 302 archival tissues of primary cutaneous melanomas from an academic comprehensive cancer center. Melanomas with BRAF mutations showed distinct morphological features such as increased upward migration and nest formation of intraepidermal melanocytes, thickening of the involved epidermis, and sharper demarcation to the surrounding skin; and they had larger, rounder, and more pigmented tumor cells (all p-values below 0.0001). By contrast, melanomas with NRAS mutations could not be distinguished based on these morphological features. Using simple combinations of features, BRAF mutation status could be predicted with up to 90.8% accuracy in the entire cohort as well as within the categories of the current World Health Organization (WHO) classification. Among the variables routinely recorded in cancer registries, we identified age < 55 y as the single most predictive factor of BRAF mutation in our cohort. Using age < 55 y as a surrogate for BRAF mutation in an independent cohort of 4,785 patients of the Southern German Tumor Registry, we found a significant survival benefit (p < 0.0001) for patients who, based on their age, were predicted to have BRAF mutant melanomas in 69% of the cases. This group also showed a different pattern of metastasis, more frequently involving regional lymph nodes, compared to the patients predicted to have no BRAF mutation and who more frequently displayed satellite, in-transit metastasis, and visceral metastasis (p < 0.0001).ConclusionsRefined morphological classification of primary melanomas can be used to improve existing melanoma classifications by forming subgroups that are genetically more homogeneous and likely to differ in important clinical variables such as outcome and pattern of metastasis. We expect this information to improve classification and facilitate stratification for therapy as well as retrospective analysis of existing trial data.

Dataset Information

The Banff Working Group Classification of Definitive Polyomavirus Nephropathy: Morphologic Definitions and Clinical Correlations.

Publications

The Banff Working Group Classification of Definitive Polyomavirus Nephropathy: Morphologic Definitions and Clinical Correlations.

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