Table 1. Results of the studies.

MM: malignant melanoma, MPM: multiphoton microscopy, OCA: optical coherence angiography, BRAF: serine/threonine-protein kinase B-Raf, CMM: cutaneous malignant melanoma, ES: elastography score, US-FNAC: ultrasound-guided fine-needle aspiration cytology, US: ultrasound, FNAC: fine-needle aspiration cytology, RCM: reflectance confocal microscopy, SPM: second primary melanoma, MDSLA: multispectral digital skin lesion analysis, SPECT/CT: single-photon emission computed tomography/computed tomography, EFI: echo-free island, PPV: positive predictive value, NPV: negative predictive value, PET/CT: positron emission tomography and computed tomography, 18F-FDG: fludeoxyglucose F18, EAR: European Association of Nuclear Medicine Research Limited

Reference	Study type	Sample size	Aim	Findings	Limitations	Recommendations
Cinotti et al., Super-high magnification dermoscopy can aid the differential diagnosis between melanoma and atypical naevi. Clin Exp Dermatol. 2021 Oct; 46(7):1216-1222 [16]	Prospective observational	79 patients	Assess the usefulness of super-high (400x) dermoscopy compared to standard (20x) dermoscopy in the diagnosis of malignant melanoma (MM)	Super-high (400X) dermoscopy was able to identify morphologic features that standard (20x) dermoscopy was unable to identify, which could be useful in the diagnosis of MM.	Sample size	Consider performing a randomized trial to evaluate the significance of the findings
Elagin et al., In vivo multimodal optical imaging of dermoscopic equivocal melanocytic skin lesions. Sci Rep. 2021 Jan 14;11(1):1405 [19]	In vivo qualitative analysis.	60 melanocytic lesions.	Determine if Multiphoton Microscopy (MPM) and Optical Coherence Angiography (OCA) can be useful positive/negative predictors for melanocytic lesions.	MPM can differentiate benign versus melanocytic lesions and OCA can differentiate invasive and non-invasive lesions.	Sample size.	Reproduce results with larger sample size across multiple healthcare systems.
Koelink et al. Diagnostic accuracy and cost-effectiveness of dermoscopy in primary care: a cluster randomized clinical trial. J Eur Acad Dermatol Venereol. 2014 Nov;28(11):1442-9 [14]	Randomized Controlled Trial.	416 lesions, 381 patients.	Determine the benefits of using dermoscopy in primary care.	Dermoscopy improves sensitivity for diagnosing melanoma up to 15% in primary care, probability of correct diagnosis is 1.25x higher but not statistically significant. Dermoscopy may reduce unnecessary referrals and biopsies and is cost-effective.	May be less applicable in the United States due to the workflow of primary care physicians.	Broaden the trial to the continental US to assess the reliability of the study.
Merkel et al. The utility of dermoscopy-guided histologic sectioning for the diagnosis of melanocytic lesions: A case-control study. Journal of the American Academy of Dermatology, 2016. 74(6), 1107–1113 [13]	Case-control.	150 melanocytic lesions.	Evaluate the diagnostic utility of dermoscopy-guided micropunch score in the evaluation of melanocytic lesions.	Dermoscopy was found to provide clinically significant information that was used to optimize the sectioning of melanocytic lesions. The authors found that regression structures, radial streaming, and irregular blotches were highly specific for a higher diagnostic grade.	Retrospective nature of case-controlled studies. Non-authentic sectioning of lesions.	Investigate the utility of the protocol in the primary analysis of melanocytic lesions in an authentic clinical setting.
Moscarella et al. Dermoscopic similarity is an independent predictor of BRAF mutational concordance in multiple melanomas. Exp Dermatol. 2019 Jul;28(7):829-835 [17]	Prospective.	124 melanomas, 62 patients.	Assess if patients with BRAF mutations exhibit dermoscopically similar melanomas.	Dermoscopically similar lesions are a positive indicator for BRAF mutations in Multiple Primary Melanoma patients.	Inherent study design lacks controlled comparisons.	Consider adjusting the study type to more rigorously assess correlation.
Mun et al. Dermoscopy of Melanomas on the Trunk and Extremities in Asians. PLoS One. 2016 Jul 8;11(7):e0158374 [11]	In vivo qualitative analysis.	22 melanocytic lesions.	Investigate the dermatoscopic patterns of melanocytic lesions on the trunk/extremities of the Asian population.	Dermoscopy can be useful in characterizing malignant melanoma among specific populations and anatomical locations.	Sample size.	Recreate study for multiple ethnicities/nationalities to characterize malignant melanoma characteristics.
Ogata et al. Accuracy of real-time ultrasound elastography in the differential diagnosis of lymph nodes in cutaneous malignant melanoma (CMM): a pilot study. Int J Clin Oncol. 2014 Aug;19(4):716-21 [8]	Prospective.	12 patients, 20 lymph nodes.	Assess the diagnostic ability of real-time elastography to differentiate between reactive and metastatic Lymph Nodes in cutaneous malignant melanoma (CMM) and to determine the optimal cut-off value to diagnose CMM.	The sensitivity, specificity, and accuracy of elastography were greater than that of B-mode ultrasound with respect to diagnosing metastatic LNs, both with an Elastography Score (ES) cutoff of 3 and 4. The optimal ES cutoff was deemed to be greater than or equal to 4.	Operator dependent. Small sample size. Subjective scoring system.	Consider repeating the study with a larger cohort and attempting to objectively quantify Elastography scores.
Oude et al. Long-term results of ultrasound guided fine needle aspiration cytology in conjunction with sentinel node biopsy support step-wise approach in melanoma. Eur J Surg Oncol. 2017 Aug;43(8):1509-1516 [6]	Cohort.	1,000 patients.	Determine the effectiveness of Ultrasound-guided Fine Needle Aspiration Cytology (US-FNAC) regarding Melanoma Specific Survival (MSS).	Positive US-FNAC patients had worse survival rates compared to those with normal US findings. Patients with normal US findings had comparable survival rates to those with suspicious US findings and a negative FNAC.	Results could diverge without expert ultrasonographers, as seen in this study.	Consider outlining the sonographic approach and repeating the study with a variety of US technicians.
Pellacani et al. Effect of Reflectance Confocal Microscopy for Suspect Lesions on Diagnostic Accuracy in Melanoma: A Randomized Clinical Trial. JAMA Dermatol. 2022 Jul 1;158(7):754-761. doi: 10.1001/jamadermatol.2022.1570. Erratum in: JAMA Dermatol. 2023 May 1;159(5):566 [3]	Randomized Controlled Trial.	3,165 patients.	Determine if Reflectance Confocal Microscopy (RCM) reduces unnecessary excision rates by 30% and determine if RCM identifies all melanoma lesions thicker than 0.5 mm.	Adjunctive  RCM for suspect lesions decreases unnecessary excisions and assures the removal of aggressive melanomas thicker than 0.5mm in a real-world scenario.	Minor reduction in reliability due to loss of follow-up/refusal of excision.	Determine characteristics that allow melanoma lesions less than 0.5mm thick to be unreliably diagnosed.
Perier-Muzet al. Melanoma patients under vemurafenib: prospective follow-up of melanocytic lesions by digital dermoscopy. J Invest Dermatol. 2014 May;134(5):1351-1358 [12]	Prospective.	2,155 melanocytic lesions.	Characterize the dermatoscopic signs of second primary melanomas (SPMs) and changes of other documented skin lesions in patients taking Vemurafenib for BRAF V600E mutations.	56.1% of documented skin lesions exhibited dermatoscopic change.	Patients lost to follow-up, sample size decreased.	Reproduce findings with different technicians and patient populations to test patterns of change and reliability of change.
Shi et al. Incorporation of dermoscopy improves inter-observer agreement among dermatopathologists in histologic assessment of melanocytic neoplasms. Arch Dermatol Res. 2021 Mar;313(2):101-108 [15]	Prospective cohort.	136 patients.	Assess whether the addition of dermoscopy to routine histopathologic analysis improves inter-observer reliability for the diagnosis of melanocytic lesions.	Inter-rater reliability with Fleiss’ kappa statistic showed an increase from 0.447 without dermoscopy to 0.496 with the addition of dermoscopy. The total atypia grade changed in 24.3% of cases after the addition of dermoscopy.	Sample size. Observer/expert size. Came from a clinic of high-risk patients so results may be more profound than the general population.	Consider retrospective analysis of erroneously diagnosed melanocytic lesions with the addition of dermoscopy to routine histopathologic analysis to assess true clinical benefit.
Soenen et al. Change in lentigo maligna score assessed by in vivo reflectance confocal microscopy after 1 month of imiquimod treatment for lentigo maligna management. J Am Acad Dermatol. 2022 May;86(5):1042-1048 [4]	Randomized Controlled Trial.	40 patients.	Assess whether Imiquimod therapy aids in the treatment of Lentigo Maligna via Reflectance Confocal Microscopy.	The Lentigo Maligna Score was significantly less in those treated with Imiquimod.	Small sample size.	Utilize Reflectance Confocal Microscopy to monitor the treatment response of immunomodulators to other melanocytic lesions.
Song et al. Paired comparison of the sensitivity and specificity of multispectral digital skin lesion analysis and reflectance confocal microscopy in the detection of melanoma in vivo: A cross-sectional study. J Am Acad Dermatol. 2016 Dec;75(6):1187-1192.e2 [5]	Cross-sectional.	36 patients, 55 lesions.	Compare the practicality of Multispectral Digital Skin Lesion Analysis (MDSLA) vs Reflectance Confocal Microscopy (RCM) in the detection of melanoma.	RCM sensitivity and specificity were 85.7% and 66.7%, respectively. MDSLA sensitivity and specificity was 71.4% and 25.0%, respectively. Both modalities can be costly, time-consuming, and operator-dependent. RCM may be more appropriate as an adjunctive diagnostic tool.	Small sample size from one dermatologist’s office.	Repeat the study with a more diverse population.
Stoffels et al. Sentinel lymph node excision with or without preoperative hybrid single-photon emission computed tomography/computed tomography (SPECT/CT) in melanoma: study protocol for a multicentric randomized controlled trial. Trials. 2019 Feb 4;20(1):99 [9]	Randomized controlled trial.	Preliminary data includes 402 patients.	Protocol aimed at determining the effectiveness of metastasis-free survival of SPECT/CT in completing sentinel node excision for melanomas.	SPECT/CT aided Sentinel Lymph Node Excision improves 5-year metastasis-free survival.	Preliminary data.	Not applicable, currently.
Voit et al. Ultrasound of the sentinel node in melanoma patients: echo-free island is a discriminatory morphologic feature for node positivity. Melanoma Research 26(3):p 267-271, June 2016 [6]	Prospective database	1000 patients.	Examine a new criterion, EFI used in ultrasound in regards to sentinel node diagnosis in melanoma	EFI was seen in 4% of patients, sensitivity and specificity were 10.8% and 97.6% respectively, PPV was 50%, and NPV was 80.2%. There is a significant correlation between EFI and peripheral perfusion. Melanoma-specific survival over 5 years was significantly worse with the presence of EFI	EFI occurrence is very rare, and US accuracy is very user dependent	Further research may be done to determine the etiology behind EFI and how it may be related to other prognostic indicators in melanoma diagnosis and management
Zengarini et al. BRAF V600K vs. BRAF V600E: a comparison of clinical and dermoscopic characteristics and response to immunotherapies and targeted therapies. Clin Exp Dermatol. 2022 Jun;47(6):1131-1136 [18]	Retrospective.	132 patients.	Compare the clinical, dermatoscopic, and prognostic features of BRAF V600E MMs and BRAF V600K MMs.	No clinical nor dermatoscopic features were able to reliably delineate between the different mutations. BRAF V600K mutations were associated with earlier metastasis and poorer response to therapy.	Small sample size, inherent limitations of retrospective studies.	Repeat the trial with a larger, prospective cohort.
Zimmermann et al. Revisiting detection of in-transit metastases in melanoma patients using digital 18F-FDG PET/CT with small-voxel reconstruction. Ann Nucl Med. 2021 Jun;35(6):669-679 [10]	Retrospective.	46 images.	Compare the effectiveness of identifying in-transit malignant melanoma (MM) metastases from the extremities with 18F-FDG PET/CT with small voxels reconstruction compared to standard reconstruction with European Association of Nuclear Medicine Research Limited (EARL) images.	Digital PET/CT with small voxel reconstruction (1mmPSF) changed 12 images from negative/intermediate to positive for in-transit metastases. Overall, the positive likelihood ratio of small-voxel reconstruction was 14.7, compared to standard reconstruction with EARL at 7.82.	Sample size, selection bias.	Compare PET/CT reconstructions in a randomized controlled trial to determine the clinical utility of small voxel reconstruction.