Figure 1
From: In vivo optical imaging-guided targeted sampling for precise diagnosis and molecular pathology

Targeted 2 mm-biopsy enables accurate tumor diagnosis. Diagnosing a suspected melanocytic lesion. (a) Clinical photograph of an ill-defined pigmented lesion concerning for lentigo maligna (melanoma in situ) on the left cheek and eyelid; (b) close-up photograph after placement of the 2-mm grid centered on the lesion (green box indicates the area targeted for biopsy after review of RCM imaging), (c) the reflective gridlines (red arrows) in addition to pigmented atypical keratinocytes (yellow asterisks) are visible in the RCM image, (d) another RCM image of the epidermis shows pigmented keratinocytes with cytological atypia sparing the adnexal structures (hair follicles) and a notable absence of a melanocytic neoplasm, indicating the presence of pigmented actinic keratosis, a precancerous lesion (instead of the original clinical indication of lentigo maligna); (e) a 2-mm biopsy of the area showing the most representative diagnostic features being performed through the window in the grid; (f) vertical frozen histopathology sections showing preserved tissue morphology (10 ×, scale bar = 300 µm); (g, h) high magnification images showing epidermal hyperpigmentation, partial-thickness keratinocytic atypia and solar elastosis confirming the RCM diagnosis of pigmented actinic keratosis (40 ×, scale bar = 50 µm). The accurate and representative nature of the RCM-guided biopsy was validated by subsequent excisional biopsy, performed as part of the standard of care, which confirmed the diagnosis as pigmented actinic keratosis. Diagnosing a suspected keratinocytic case. (i) Clinical photograph of a pigmented lesion clinically suspected to be a basal cell carcinoma; (j) dermoscopic photograph after placement of the 2-mm grid centered on the lesion (green box indicates the area targeted for biopsy after review of RCM imaging); (k) RCM image reveals basaloid tumor islands showing peripheral palisading and a dark rim of mucin (heart-shaped tumor in yellow dotted rectangle); (l), 2-mm punch through the grid followed by preparation of horizontal histopathology sections that confirm the presence of BCC (10x, scale bar = 300 µm); (m) the inset highlights the heart shaped tumor island seen in RCM images (40 ×, scale bar = 30 µm). This experiment establishes the proof-of-concept for spatial targeting and illustrates accurate diagnostic pathology with high-resolution imaging-guided precision biopsy and minimally invasive sampling.