Sclerosing stromal tumor of the ovary a case series and review of literature

Sclerosing stromal tumor of the ovary is a rare benign sex-cord stromal tumor that affects primarily young females. In a series of 6 patients (mean 24,6, median 19 years) findings of 6 MRIs and 1 CT were analyzed. Unilateral tumors ranging from 6 to 8 cm were found in all patients. The tumors were well encapsulated and polylobulated. The morphology was mixed solid and cystic in three and solid in 3 patients. In CT, a hypervascular tumor with centripetal enhancement was seen. In MRI T2WI showed low signal intensity of the solid tissue in all cases and low DWI signal of the solid tissue in high b value DWI in 3 patients. Contrast enhancement was avid with extension from the periphery in all patients. Knowledge of these distinct radiological features of sclerosing stromal tumor is important, as in the O-RADS risk classification system this may be scored as O-RADS 5. Because of its non-aggressive clinical course, preoperative imaging assists to avoid unnecessary extensive surgery and to preserve the patient’s fertility by only resecting the tumor and preserving the ovary. Sclerosing stromal tumor of the ovary presents pathognomonic features in MRI that allow a specific preoperative diagnosis and selecting candidates for fertility-sparing surgery.

Enhancing Checkpoint Inhibitor Therapy in Solid Tissue Cancers: The Role of Diet, the Microbiome & Microbiome-Derived Metabolites

Host immunity plays a central role in the regulation of anti-tumour responses during checkpoint inhibitor therapy (CIT). The mechanisms involved in long lasting remission remain unclear. Animal studies have revealed that the microbiome influences the host immune response. This is supported by human studies linking a higher microbial richness and diversity with enhanced responses to CIT. This review focuses on the role of diet, the microbiome and the microbiome-derived metabolome in enhancing responses to current CIT in solid tissue cancers. The Western diet has been associated with dysbiosis, inflammation and numerous metabolic disorders. There is preliminary evidence that lifestyle factors including a high fibre diet are associated with improved responses to CIT via a potential effect on the microbiota. The mechanisms through which the microbiota may regulate long-term immunotherapy responses have yet to be determined, although bacterial-metabolites including short chain fatty acids (SCFAs) are recognized to have an impact on T cell differentiation, and may affect T effector/regulatory T cell balance. SCFAs were also shown to enhance the memory potential of activated CD8 T cells. Many therapeutic approaches including dietary manipulation and fecal transplantation are currently being explored in order to enhance immunotherapy responses. The microbiome-derived metabolome may be one means through which bacterial metabolic products can be monitored from the start of treatment and could be used to identify patients at risk of poor immunotherapy responses. The current review will discuss recent advances and bring together literature from related fields in nutrition, oncology and immunology to discuss possible means of modulating immunity to improve responses to current CIT.

Translation of a circulating miRNA signature of melanoma into a solid tissue assay to improve diagnostic accuracy and precision

Aim: Successful treatment of cutaneous melanoma depends on early and accurate diagnosis of clinically suspicious melanocytic skin lesions. Multiple international studies have described the challenge of providing accurate and reproducible histopathological assessments of melanocytic lesions, highlighting the need for new diagnostic tools including disease-specific biomarkers. Previously, a 38-miRNA signature (MEL38) was identified in melanoma patient plasma and validated as a novel biomarker. In this study, MEL38 expression in solid tissue biopsies representing the benign nevi to metastatic melanoma spectrum is examined. Patients & methods: Nanostring digital gene expression assessment of the MEL38 signature was performed on 308 formalin-fixed paraffin-embedded biopsies of nevi, melanoma in situ and invasive melanoma. Genomic data were interrogated using hierarchical clustering, univariate and multivariate statistical approaches. Classification scores computed from the MEL38 signature were analyzed for their association with demographic data and histopathology results, including MPATH-DX class, AJCC disease stage and tissue subtype. Results: The MEL38 score can stratify higher-risk melanomas (MPATH-Dx class V or more advanced) from lower-risk skin lesions (class I–IV) with an area under the curve of 0.97 (p < 0.001). The genomic score ranges from 0 to 10 and is positively correlated with melanoma progression, with an intraclass correlation coefficient of 0.85 with stage 0–IV disease. Using an optimized classification threshold of ≥2.7 accurately identifies higher-risk melanomas with 89% sensitivity and 94% specificity. Multivariate analysis showed the score to be a significant predictor of malignancy, independent of technical and clinical covariates. Application of the MEL38 signature to Spitz nevi reveals an intrasubtype profile, with elements in common to both nevi and melanoma. Conclusion: Melanoma-specific circulating miRNAs maintain their association with malignancy when measured in the hypothesized tissue of origin. The MEL38 signature is an accurate and reproducible metric of melanoma status, based on changes in miRNA expression that occur as the disease develops and spreads. Inclusion of the MEL38 score into routine practice would provide physicians with previously unavailable, personalized genomic information about their patient’s skin lesions. Combining molecular biomarker data with conventional histopathology data may improve diagnostic accuracy, healthcare resource utilization and patient outcomes.

Translation of a circulating microRNA signature of melanoma into a solid tissue assay to improve diagnostic accuracy and precision.

Background: Successful treatment of cutaneous melanoma depends on early and accurate diagnosis of clinically suspicious melanocytic skin lesions. Multiple international studies have described the challenge of providing accurate and reproducible histopathological assessments of melanocytic lesions, highlighting the need for new diagnostic tools including disease-specific biomarkers. Previously, a 38-microRNA signature (“MEL38”) was identified in melanoma patient plasma and validated as a novel biomarker. In this study, MEL38 expression in solid tissue biopsies representing the benign naevi to metastatic melanoma spectrum is examined. Methods: Nanostring digital gene expression assessment of the MEL38 signature was performed on 308 formalin fixed paraffin embedded biopsies of naevi, melanoma in-situ and invasive melanoma. Genomic data were interrogated using hierarchical clustering, univariate, and multivariate statistical approaches. Classification scores computed from the MEL38 signature were analysed for their association with demographic data and histopathology results, including MPATH-DX class, AJCC disease stage and tissue subtype. Results: The MEL38 score can stratify higher-risk melanomas (MPATH-Dx Class V or more advanced) from lower-risk skin lesions (Class I-IV) with an area-under-the curve of 0.97 (P<0.001). The genomic score ranges from 0 to 10 and is positively correlated with melanoma progression, with an intraclass correlation coefficient of 0.85 with stage 0 to IV disease. Using an optimised classification threshold of ≥2.7 accurately identifies higher-risk melanomas, associated with poorer outcomes and more intensive suggested clinical actions with 89% sensitivity and 94% specificity. Multivariate analysis showed the score to be a significant predictor of malignancy, independent of technical and clinical covariates. Application of the MEL38 signature to spitz naevi reveal an intra-subtype profile, with elements of the profile in common to both naevi and melanoma. Conclusion: Melanoma-specific circulating microRNAs maintain their association with malignancy when measured in the hypothesized tissue of origin. The MEL38 signature is an accurate and reproducible metric of melanoma status, based on changes in microRNA expression that occur as the disease develops and spreads. Inclusion of the MEL38 score into routine practice would provide physicians with previously unavailable, personalised genomic information about their patient’s skin lesions. Combining molecular biomarker data with conventional histopathology data may improve diagnostic accuracy, healthcare resource utilisation, and patient outcomes.

Translation of a circulating microRNA signature of melanoma into a solid tissue assay with the potential to improve diagnostic precision and reproducibility

Background: Successful treatment of cutaneous melanoma depends on early and accurate diagnosis of clinically suspicious melanocytic skin lesions. Multiple international studies have described the challenge of providing accurate and reproducible histopathological assessments of melanocytic lesions, highlighting the need for new diagnostic tools including disease-specific biomarkers. Previously, a 38-microRNA signature (“MEL38”) was identified in melanoma patient plasma and validated as a novel biomarker. In this study, MEL38 expression in solid tissue biopsies representing the benign naevi to metastatic melanoma spectrum is examined. Methods: Nanostring digital gene expression assessment of the MEL38 signature was performed on 308 formalin fixed paraffin embedded biopsies of naevi, melanoma in-situ and invasive melanoma. Genomic data were interrogated using hierarchical clustering, univariate, and multivariate statistical approaches. Classification scores computed from the MEL38 signature were analysed for their association with demographic data and histopathology results, including MPATH-DX class, AJCC disease stage and tissue subtype. Results: The MEL38 score can stratify higher-risk melanomas (MPATH-Dx Class V or more advanced) from lower-risk skin lesions (Class I-IV) with an area-under-the curve of 0.97 (P<0.001). The genomic score ranges from 0 to 10 and is positively correlated with melanoma progression, with an intraclass correlation coefficient of 0.85 with stage 0 to IV disease. Using an optimised classification threshold of ≥2.7 accurately identifies higher-risk melanomas, associated with poorer outcomes and more intensive suggested clinical actions with 89% sensitivity and 94% specificity. Multivariate analysis showed the score to be a significant predictor of malignancy, independent of technical and clinical covariates. Application of the MEL38 signature to spitz naevi reveal an intra-subtype profile, with elements of the profile in common to both naevi and melanoma. Conclusion: Melanoma-specific circulating microRNAs maintain their association with malignancy when measured in the hypothesized tissue of origin. The MEL38 signature is an accurate and reproducible metric of melanoma status, based on changes in microRNA expression that occur as the disease develops and spreads. Inclusion of the MEL38 score into routine practice would provide physicians with previously unavailable, personalised genomic information about their patient’s skin lesions. Combining molecular biomarker data with conventional histopathology data may improve diagnostic accuracy, healthcare resource utilisation, and patient outcomes.

Translation of a circulating microRNA signature of melanoma into a solid tissue assay with the potential to improve diagnostic precision and reproducibility

Background: Successful treatment of cutaneous melanoma depends on early and accurate diagnosis of clinically suspicious melanocytic skin lesions. Multiple international studies have described the challenge of providing accurate and reproducible histopathological assessments of melanocytic lesions, highlighting the need for new diagnostic tools including disease-specific biomarkers. Previously, a 38-microRNA signature (“Mel38”) was identified in melanoma patient plasma and validated as a novel biomarker. In this study, Mel38 expression in solid tissue biopsies representing the benign naevi to metastatic melanoma spectrum is examined. Methods: Nanostring digital gene expression assessment of the Mel38 signature was performed on 308 formalin fixed paraffin embedded biopsies of naevi, melanoma in-situ and invasive melanoma. Genomic data were interrogated using hierarchical clustering, univariate, and multivariate statistical approaches. Classification scores computed from the Mel38 signature were analysed for their association with demographic data and histopathology results, including MPATH-DX class, AJCC disease stage and tissue subtype. Results: The Mel38 score can stratify higher-risk melanomas (MPATH-Dx Class V or more advanced) from lower-risk skin lesions (Class I-IV) with an area-under-the curve of 0.97 (P<0.001). The genomic score ranges from 0 to 10 and is positively correlated with melanoma progression, with an intraclass correlation coefficient of 0.85 with stage 0 to IV disease. Using an optimised classification threshold of ≥2.7 accurately identifies higher-risk melanomas, associated with poorer outcomes and more intensive suggested clinical actions with 89% sensitivity and 94% specificity. Multivariate analysis showed the score to be a significant predictor of malignancy, independent of technical and clinical covariates. Application of the Mel38 signature to spitz naevi reveal an intra-subtype profile, with elements of the profile in common to both naevi and melanoma. Conclusion: Melanoma-specific circulating microRNAs maintain their association with malignancy when measured in the hypothesized tissue of origin. The Mel38 signature is an accurate and reproducible metric of melanoma status, based on changes in microRNA expression that occur as the disease develops and spreads. Inclusion of the Mel38 score into routine practice would provide physicians with previously unavailable, personalised genomic information about their patient’s skin lesions. Combining molecular biomarker data with conventional histopathology data may improve diagnostic accuracy, healthcare resource utilisation, and patient outcomes.

Translation of a circulating melanoma microRNA profile into a solid tissue assay to improve diagnostic accuracy

Background: Successful treatment of cutaneous melanoma depends on early and accurate diagnosis of clinically suspicious melanocytic skin lesions. Multiple international studies have described the challenge of providing accurate and reproducible histopathological assessments of melanocytic lesions, highlighting the need for new diagnostic tools including disease-specific biomarkers. Previously, a 38-microRNA signature (“Mel38”) was identified in melanoma patient plasma and validated as a novel biomarker. In this study, Mel38 expression in solid tissue biopsies representing the benign naevi to metastatic melanoma spectrum is examined. Methods: Nanostring digital gene expression assessment of the Mel38 signature was performed on 308 formalin fixed paraffin embedded biopsies of naevi, melanoma in-situ and invasive melanoma. Genomic data were interrogated using hierarchical clustering, univariate, and multivariate statistical approaches. Classification scores computed from the Mel38 signature were analysed for their association with demographic data and histopathology results, including MPATH-DX class, AJCC disease stage and tissue subtype. Results: The Mel38 score can stratify higher-risk melanomas (MPATH-Dx Class V or more advanced) from lower-risk skin lesions (Class I-IV) with an area-under-the curve of 0.96 (P<0.001). The genomic score ranges from 0 to 10 and is positively correlated with melanoma progression, with an intraclass correlation coefficient of 0.85 with stage 0 to IV disease. Using an optimised classification threshold of ≥2.3 accurately identifies higher-risk melanomas, associated with poorer outcomes and more intensive suggested clinical actions with 95% sensitivity and 83% specificity. Multivariate analysis showed the score to be a significant predictor of malignancy, independent of technical and clinical covariates. Application of the Mel38 signature to spitz naevi reveal an intra-subtype profile, with elements of the profile in common to both naevi and melanoma. Conclusion: Melanoma-specific circulating microRNAs maintain their association with malignancy when measured in the hypothesized tissue of origin. The Mel38 signature is an accurate and reproducible metric of melanoma status, based on changes in microRNA expression that occur as the disease develops and spreads. Inclusion of the Mel38 score into routine practice would provide physicians with previously unavailable, personalised genomic information about their patient’s skin lesions. Combining molecular biomarker data with conventional histopathology data may improve diagnostic accuracy, healthcare resource utilisation, and patient outcomes.

Mechanical control of tissue shape and morphogenetic flows during vertebrate body axis elongation

Shaping embryonic tissues into their functional morphologies requires cells to control the physical state of the tissue in space and time. While regional variations in cellular forces or cell proliferation have been typically assumed to be the main physical factors controlling tissue morphogenesis, recent experiments have revealed that spatial variations in the tissue physical (fluid/solid) state play a key role in shaping embryonic tissues. Here we theoretically study how the regional control of fluid and solid tissue states guides morphogenetic flows to shape the extending vertebrate body axis. Our results show that both the existence of a fluid-to-solid tissue transition along the anteroposterior axis and the tissue surface tension determine the shape of the tissue and its ability to elongate unidirectionally, with large tissue tensions preventing unidirectional elongation and promoting blob-like tissue expansions. We predict both the tissue morphogenetic flows and stresses that enable unidirectional axis elongation. Our results show the existence of a sharp transition in the structure of morphogenetic flows, from a flow with no vortices to a flow with two counter-rotating vortices, caused by a transition in the number and location of topological defects in the flow field. Finally, comparing the theoretical predictions to quantitative measurements of both tissue flows and shape during zebrafish body axis elongation, we show that the observed morphogenetic events can be explained by the existence of a fluid-to-solid tissue transition along the anteroposterior axis. These results highlight the role of spatiotemporally-controlled fluid-to-solid transitions in the tissue state as a physical mechanism of embryonic morphogenesis.