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. 2019 Nov 22;6:274. doi: 10.3389/fmed.2019.00274

Table 6.

Key articles comparing multiphoton microscopy and histopathology.

Tumor type Year Type Main findings Correlation with histopathological findings Sample size
Basal cell carcinoma (BCC) (39) 2015 In vivo multiphoton microscopy (MPM) 1. Nests of basaloid cells palisading in the peripheral cell layer at the dermoepidermal junction and/or in the dermis
2. Parallel collagen and elastin bundles surrounding the tumors
3. Mucinous stroma adjacent to tumor was visualized using MPM
These features generally correlated well with histopathologic examination. However, histologic examination revealed palisading of peripheral layers in some of the tumor nests of the lesion, although this feature was not obvious in the nests imaged with MPM. 9 patients with a total of 10 BCC
Squamous cell carcinoma in situ (SCCIS), superfical BCC (SBCC) (40) 2008 Ex vivo MPM The following findings were seen: SCCIS: bowenoid dysplasia, multinucleated cells, or hyperkeratosis SBCC: peripheral palisading of tumor cells The morphologic features differed significantly between these lesions and perilesional skin. 5 specimens of SCCIS
6 specimens of SBCC
Actinic keratosis (AK), squamous cell carcinoma (SCC) (41) 2016 In vivo MPM Changes in the morphology of the keratinocytes, such as broadened epidermis, large intercellular spaces, enlarged nucleus and a large variance in cell shape could easily be recognized. AK: hyperparakeratosis and cell pleomorphism
SCC: invasion of the dermis, keratin pearls and hyperchromatic nuclei
6 patients with AK
6 patients with SCC
Benign and malignant melanocytic nevi (BMMN) (42) 2014 In vivo MPM They evaluate BMMN using 9-point scale showing different values according to two-photon excited fluorescence and second harmonic generation of nevi. Indices corresponding to common nevi (0–1), dysplastic nevi (1-4), and melanoma (5-8) were significantly different (P < 0.05). Prominent qualitative correlations included the morphology of epidermal keratinocytes, the appearance of nests of nevus cells surrounded by collagen fibers, and the structure of the epidermal–dermal junction. 5 common nevi
5 dysplastic nevi
5 melanoma
BCC, SCC, dermatofibrosarcoma protuberans (DFSP) (43) 2019 Ex vivo moxifloxacin labeling-based MPM Moxifloxacin MPM imaged both cells and collagen in the skin, similarly to label-free MPM, but with enhanced fluorescence intensities in cells and enhanced imaging speeds. Moxifloxacin MPM could detect specific cellular features of various skin cancers in good correlation with histopathological images at the higher imaging speed than label-free MPM. 10 patients with BCC
1 patient with SCC
1 patient with DFSP