In Vivo Reflectance Confocal Microscopy as a Response Monitoring Tool for Actinic Keratoses Undergoing Cryotherapy and Photodynamic Therapy.

Reflectance confocal microscopy (RCM) presents a non-invasive method to image actinic keratosis (AK) at a cellular level. However, RCM criteria for AK response monitoring vary across studies and a universal, standardized approach is lacking. We aimed to identify reliable AK response criteria and to compare the clinical and RCM evaluation of responses across AK severity grades. Twenty patients were included and randomized to receive either cryotherapy (n = 10) or PDT (n = 10). Clinical assessment and RCM evaluation of 12 criteria were performed in AK lesions and photodamaged skin at baseline, 3 and 6 months. We identified the RCM criteria that reliably characterize AK at baseline and display significant reduction following treatment. Those with the highest baseline odds ratio (OR), good interobserver agreement, and most significant change over time were atypical honeycomb pattern (OR: 12.7, CI: 5.7-28.1), hyperkeratosis (OR: 13.6, CI: 5.3-34.9), stratum corneum disruption (OR: 7.8, CI: 3.5-17.3), and disarranged epidermal pattern (OR: 6.5, CI: 2.9-14.8). Clinical evaluation demonstrated a significant treatment response without relapse. However, in grade 2 AK, 10/12 RCM parameters increased from 3 to 6 months, which suggested early subclinical recurrence detection by RCM. Incorporating standardized RCM protocols for the assessment of AK may enable a more meaningful comparison across clinical trials, while allowing for the early detection of relapses and evaluation of biological responses to therapy over time.

Lichen planus-like keratosis: clinical applicability of in vivo reflectance confocal microscopy for an indeterminate cutaneous lesion.

Lichen planus-like keratosis (LPLK) is an involuting cutaneous lesion often presenting between the fifth and seventh decades of life. These lesions typically appear abruptly as a solitary macule, papule, or plaque that continuously evolves as it undergoes regression. Clinical and dermoscopic features of LPLK can mimic both benign and malignant lesions, often prompting biopsy for accurate diagnosis. We describe a case of LPLK developing in a patient with a history of multiple skin cancers, including melanoma. Dermoscopy revealed peripheral granules and a central area with pinkish-brown pigmentation and a disorganized pattern with shiny white structures and rosettes. Handheld reflectance confocal microscopy (RCM) showed a typical honeycomb pattern with millia-like cysts and comedo-like openings, and lacked pagetoid and dendritic cells. Based on the benign features seen with RCM, the lesion was followed until complete regression was observed. In conclusion, we describe a case of LPLK with clinically and dermoscopically indeterminate features that was successfully monitored with RCM. We intend to highlight the utility of RCM as a diagnostic aid in equivocal lesions in order to prevent unnecessary excisional procedures.

Accuracy and confidence in the clinical diagnosis of basal cell cancer using dermoscopy and reflex confocal microscopy.

BACKGROUND: Diagnosis of suspected basal cell carcinoma (BCC) is typically confirmed with incisional biopsy before referral to final surgery. OBJECTIVE: To investigate the clinical confidence and accuracy of physicians making a diagnosis of BCC based on dermoscopic and reflectance confocal microscopy (RCM) features. METHODS: This study was designed as a simulation to determine the certainty and willingness to refer to surgery without previous biopsy confirmation of BCC. Study subjects were identified with suspected BCC. Dermoscopic and RCM lesion images were obtained before biopsy. Eight clinicians with various expertise levels blindly interpreted these images and chose among four hypothetical treatment options: definite BCC, refer directly to surgery without biopsy; other malignancy, perform biopsy for diagnosis; uncertain diagnosis, perform biopsy; benign, do not biopsy. Decisions for treatment were based on dermoscopic images alone and, subsequently, on dermoscopic and RCM images combined. RESULTS: The sensitivity for referral to surgery without biopsy was 67.6% with the use of dermoscopy; the positive predictive value (PPV) was 97.0%. Adding RCM increased the sensitivity to 76.5% and the PPV to 98.6%. CONCLUSIONS: Dermoscopy provides a high PPV for BCC. The addition of RCM to dermoscopy increases diagnostic sensitivity, particularly in less experienced dermoscopists. Physician behavior might be different if actual referrals were made for surgery without biopsy.

Dark homogeneous streak dermoscopic pattern correlating with specific KIT mutations in melanoma.

IMPORTANCE: Mutations driving melanoma growth have diagnostic, prognostic, and therapeutic implications. Traditional classification systems do not correlate optimally with underlying melanoma growth-promoting mutations. Our objective was to determine whether unique dermoscopic growth patterns directly correlate with driving mutations. OBSERVATIONS: We evaluated common driving mutations in 4 different dermoscopic patterns (rhomboidal, negative pigmented network, polygonal, and dark homogeneous streaks) of primary cutaneous melanomas; 3 melanomas per pattern were tested. Three of the 4 patterns lacked common mutations in BRAF, NRAS, KIT, GNAQ, and HRAS. One pattern, the dark homogeneous streaks pattern, had unique KIT mutations in the second catalytic domain of KIT in exon 17 for all 3 samples tested. Two tumors with the dark homogeneous streaks pattern turned out to be different primary melanomas from the same patient and had different sequence mutations but had an impact on the same KIT domain. CONCLUSIONS AND RELEVANCE: While future study is required, these results have multiple implications. (1) The underlying melanoma-driving mutations may give rise to specific dermoscopic growth patterns, (2) BRAF/NRAS mutations in early melanomas may not be as common as previously thought, and (3) patients may be predisposed to developing specific driving mutations giving rise to melanomas or nevi of similar growth patterns.

The role of reflectance confocal microscopy as an aid in the diagnosis of collision tumors.

BACKGROUND: The term 'collision tumor' refers to the association of 2 or more different neoplasms within the same lesion. The association of a benign neoplasm with a malignant neoplasm is of particular significance and warrants diagnostic accuracy. OBJECTIVE: The purpose of our study was to see if reflectance confocal microscopy (RCM) was a valuable tool when dealing with collision tumors. METHODS: We retrospectively evaluated 24 histologically confirmed cases of collision tumors, which were initially assessed using dermoscopy and RCM. RESULTS: The malignancy most commonly detected in association with collision tumors was basal cell carcinoma (BCC) (n = 13), followed by melanoma (n = 5, of which 2 collided with BCC) and squamous cell carcinoma in situ (n = 4). Seborrheic keratoses were the most common benign neoplasms found in association with collision tumors (n = 18), followed by nevi (n = 7). Dermoscopy revealed the malignant component in 14 out of 20 lesions compared to RCM, which revealed a malignant component in 19 out of 20 neoplasms. There was excellent concordance between RCM and histopathology with regard to the identification of a malignant component within a tumor (kappa value >0.9). CONCLUSION: The dermatoscope and the reflectance confocal microscope, when used in conjunction, are valuable tools aiding in the diagnosis of collision tumors.

Influence of time on dermoscopic diagnosis and management.

BACKGROUND/OBJECTIVES: Dermoscopy aids in clinical decision-making. However, time pressure is a common reason precluding its use. We evaluated the effect of time on lesion recognition and management decisions utilising clinical and dermoscopic images. METHOD: In all, 100 dermoscopic images were presented to 15 dermatologists with experience in dermoscopy and seven non-experts (dermatology residents). Each lesion was displayed thrice in succession. The dermoscopic image was initially presented for 1 s (t1). The same dermoscopic image was shown again without time constraints (t2) and then a final time with additional images of the clinical context (t3). Participants provided a diagnosis, their level of confidence and biopsy predilection after evaluating each image. RESULTS: For benign lesions, both groups rarely changed their diagnosis. However, an improvement in the number of correct benign diagnoses was observed when the lesion was shown in a clinical context. For malignant lesions, both groups improved when more time and clinical context was given; nevertheless, non-experts were more likely to change the diagnosis towards the correct one as more time was given and tended to perform more biopsies, in particular of benign lesions. Limitations were a small number of participants and an artificial study setting. CONCLUSION: Dermoscopy uses analytical and non-analytical reasoning approaches. We suggest that non-analytical reasoning is employed when rapid clinical decisions need to be made, especially during the evaluation of benign lesions. We conclude that dermoscopy is relatively rapid and non-time-consuming technique that adds relevant information and guides clinicians towards appropriate management decisions.

Reflectance confocal microscopy criteria for squamous cell carcinomas and actinic keratoses.

OBJECTIVE: To identify criteria for the diagnosis of squamous cell carcinoma (SCC) and actinic keratosis (AK) by in vivo reflectance confocal microscopy (RCM). DESIGN: Prospective RCM imaging of lesions suspected clinically and/or dermoscopically to be SCC or AK, followed by RCM assessment of the biopsy-proven SCCs and AKs. SETTING: Private skin cancer clinic, Plantation, Florida. Patients A total of 38 lesions in 24 patients were assessed, including 7 AKs, 25 SCCs in situ, 3 invasive SCCs, and 3 keratoacanthomas. Interventions Prior to undergoing biopsy, all lesions were assessed by RCM. RESULTS: Mosaic RCM images at the stratum corneum level revealed scale in 29 SCCs (95%) and in all 7 AKs. Polygonal nucleated cells at the stratum corneum were seen in 3 SCCs (10%) and 1 AK (14%). All 38 cases displayed an atypical honeycomb and/or a disarranged pattern of the spinous-granular layer of the epidermis; round nucleated cells were seen in the spinous-granular layer in 20 SCCs (65%) and 1 AK (14%). Round blood vessels in the superficial dermis were seen in 28 SCCs (90%) and 5 AKs (72%). CONCLUSIONS: An increasing frequency of abnormal RCM features can be observed across the spectrum of keratinocytic neoplasias. The presence of an atypical honeycomb or a disarranged pattern of the spinous-granular layer, round nucleated cells at the spinous-granular layer, and round blood vessels traversing through the dermal papilla are the key RCM features of SCC.

How to diagnose malignant melanoma.

The incidence of malignant melanoma has increased dramatically in recent decades. Although curable if caught early, malignant melanoma often presents a diagnostic challenge. This article discusses modalities for identifying malignant melanoma, including four techniques used in skin examinations: (1) ABCD method, (2) total-body photography, (3) skin surface microscopy, and (4) machine vision.