Optical imaging guided- ‘precision’ biopsy of skin tumors: a novel approach for targeted sampling and histopathologic correlation

Navarrete‐Dechent, Cristián; Córdova, Miguel; Sahu, Aditi; Liopyris, Konstantinos; Rishpon, Ayelet; Chen, Curtis; Rajadhyaksha, Milind; Busam, Klaus J.; Marghoob, Ashfaq A.; Chen, Chih‐Shan Jason

doi:10.1007/s00403-020-02126-6

Cited by 15 publications

(15 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prior studies on non-targeted biopsies have demonstrated the feasibility of 0.33-0.5 mm biopsies for histology, ultrastructural analysis, and gene expressions evaluation in a few genes (13,14), and RCMguided 2-mm biopsy for histopathology using paper-rings (15). The ndings from our study demonstrate the ability to perform imaging-guided 1-mm targeted biopsy for downstream diagnosis (by preserving tissue architecture) and next-generation molecular pro ling (by ensuring high nucleic acid quality and quantity) in both in vivo and ex vivo settings.…”

Section: Resultsmentioning

confidence: 99%

In Vivo Optical Imaging-Guided Targeted Sampling for Precise Diagnosis and Molecular Pathology

Sahu¹,

Peterson²,

Córdova³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Conventional tissue sampling used in disease and cancer diagnosis can lead to misdiagnoses and repeated biopsies, and the tissue processed for histopathology suffers from poor nucleic acid quality/quantity for molecular profiling. Targeted micro-sampling of tissue can ensure accurate diagnosis and molecular profiling in the presence of spatial heterogeneity and complexity, especially in tumors, and facilitate acquisition of fresh tissue for molecular analysis. In this study, we explored the feasibility of a 1-mm precision biopsy approach guided by high-resolution reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) imaging, and reflective metallic grids for accurate spatial targeting and sampling in 7 skin cancers lesions in 6 patients. Accurate sampling was confirmed by histopathology or successful molecular profiling using next generation sequencing (NGS) approaches. Imaging guided 1-mm biopsy enabled spatial targeting and sampling for in vivo diagnosis, feature correlation and predicted depth as confirmed on histopathology. High DNA quantity (680 ng) and quality (DIN: 8) were obtained from imaging-guided high melanoma cell density areas. Subsequent mutational profiling on a 505-gene panel revealed a missense BRAF V600E oncogenic mutations at 0.02 allelic frequency for guiding therapy. Our findings demonstrate accurate sampling of regions of interest that enables downstream diagnosis, molecular analysis and research in both in vivo and ex vivo settings with broad diagnostic, therapeutic and research potential in dermatological and mucosal settings currently accessible to RCM-OCT imaging.

show abstract

Section: Resultsmentioning

confidence: 99%

In Vivo Optical Imaging-Guided Targeted Sampling for Precise Diagnosis and Molecular Pathology

Sahu¹,

Peterson²,

Córdova³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…With the current state of RCM devices and technology, this approach is currently restricted to accessible diseases and cancers, namely skin cancer, head-neck cancer, cervical cancers, cutaneous lymphomas, cutaneous metastasis. In the future, extensive validation with targeted molecular correlations on precision biopsies 42 will enable better correlations. Exhaustive molecular validation using flow cytometry and single-cell RNA-seq and spatial transcriptomics 43,44 on subsequent models will facilitate improved understanding of RCM phenotyping.…”

Section: Discussionmentioning

confidence: 99%

Cellular-level phenotyping of tumor-immune microenvironment (TiME) in patients in vivo reveals distinct inflammation and endothelial anergy signatures

Sahu

Tembo

Kose

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Immunotherapies, especially immune checkpoint blockade therapy have shown unprecedented clinical benefits in several malignancies, however, responses are variable emphasizing the need for effective biomarkers for patient stratification1. Phenotyping of tumors into hot, altered, or cold2 based on T-lymphocyte infiltration in tumor biopsies fails to explain and/or predict response to immunotherapy seen in a subset of patients3,4. One of the primary reasons for this suboptimal prediction by a single immune marker could be attributed to the fact that additional mechanisms within the tumor microenvironment modulate anti-tumor immunity and outcomes, including dynamic events such as tumor-angiogenesis and leukocyte trafficking2,5,6. We report novel tumor phenotypes through non-invasive spatially-resolved cellular-level analysis of the tumor immune microenvironment (TiME) and major determinants of anti-tumor immunity. Using skin cancers as a model and optical imaging using reflectance confocal microscopy (RCM)7, we determined four major phenotypes based on unsupervised clustering for relative prevalence of vasculature (Vasc) and inflammation (Inf) features: VaschighInfhigh, VaschighInflow, VasclowInf(intratumoral)high and VascmodInflow. The VaschighInfhigh phenotype correlate with high immune and vascular signatures while VaschighInflow with endothelial anergy. Automated quantification of TiME features demonstrates moderate accuracy and high correlation with corresponding gene expression. Prospective testing of TiME features prior to topical immunotherapy response shows highest response in the VasclowInf(IT)high phenotype, and revealing the added value of vascular features in predicting treatment response. This novel in vivo phenotyping combining dynamic immune and vascular features has the potential to advance fundamental understanding of the highly dynamic TiME, identify novel druggable pathways and develop robust predictors for immunotherapy outcomes.

show abstract

“…It remains unclear if the negative network seen in NAMs represents the nevus remnant or the site of melanoma progression, as precision biopsies targeting this feature were not conducted in this study. 5 If the former, the feature might prove useful as a biomarker to predict future risk of melanoma transformation among nevi. If the latter, characterization of the molecular alterations present in melanocytes of negative network may yield novel insights into tumour progression.…”

Section: Unveiling Melanomagenesis Through the Dermatoscopementioning

confidence: 99%

“…Unlike prior studies, no other dermatoscopic features, including those associated with nevi, showed a difference in NAMs compared with DNMs. It remains unclear if the negative network seen in NAMs represents the nevus remnant or the site of melanoma progression, as precision biopsies targeting this feature were not conducted in this study 5 . If the former, the feature might prove useful as a biomarker to predict future risk of melanoma transformation among nevi.…”

mentioning

confidence: 97%

“…Thus, a young patient with fair skin, multiple nevi and one dermoscopically outlier lesion on the trunk revealing a negative network will probably require a skin biopsy to rule out a NAM. If histopathology does not demonstrate a melanoma, careful clinical–pathological correlation with step‐sectioning should be considered, as a foci of melanoma might have been missed 5 . On the other hand, in a young patient with fair skin, and multiple nevi with a predominant pattern of negative network, careful monitoring with digital dermoscopy could alternatively be considered.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Unveiling melanomagenesis through the dermatoscope

Navarrete‐Dechent

Jaimes

Marchetti

2021

Acad Dermatol Venereol

Self Cite

View full text Add to dashboard Cite

show abstract

Optical imaging guided- ‘precision’ biopsy of skin tumors: a novel approach for targeted sampling and histopathologic correlation

Cited by 15 publications

References 45 publications

In Vivo Optical Imaging-Guided Targeted Sampling for Precise Diagnosis and Molecular Pathology

In Vivo Optical Imaging-Guided Targeted Sampling for Precise Diagnosis and Molecular Pathology

Cellular-level phenotyping of tumor-immune microenvironment (TiME) in patients in vivo reveals distinct inflammation and endothelial anergy signatures

Unveiling melanomagenesis through the dermatoscope

Contact Info

Product

Resources

About