Search Results (67)

Mammary Paget disease (MPD) is a rare cutaneous malignancy associated with underlying ductal carcinoma in situ (DCIS) or invasive ductal carcinoma (IDC). Clinically, it appears as eczematous changes in the nipple and areola complex (NAC), which may include itching, redness, crusting, and ulceration; these symptoms can sometimes mimic benign dermatologic conditions such as nipple eczema, making early diagnosis challenging. A 56-year-old woman presented with persistent erythema and scaling of the left nipple, which did not respond to conventional dermatologic treatments: a high degree of suspicion prompted further investigation. Reflectance confocal microscopy (RCM) revealed atypical, enlarged epidermal cells with irregular boundaries, while line-field confocal–optical coherence tomography (LC-OCT) demonstrated thickening of the epidermis, hypo-reflective vacuous spaces and abnormally large round cells (Paget cells). These non-invasive imaging findings were consistent with an aggressive case of Paget disease despite the absence of clear mammographic evidence of underlying carcinoma: in fact, several biopsies were needed, and at the end, massive surgery was necessary. Non-invasive imaging techniques, such as dermoscopy, RCM, and LC-OCT, offer a valuable diagnostic tool in detecting Paget disease, especially in early stages and atypical forms. Full article

Penile intraepithelial neoplasia (PeIN) is a rare but clinically significant condition that can progress to invasive squamous carcinoma. Early diagnosis is crucial but often challenging due to its heterogeneous clinical and dermoscopic presentation, which can mimic other benign or malignant lesions. In this study, we report two cases of pigmented penile lesions evaluated using non-invasive imaging techniques: reflectance confocal microscopy (RCM) and line-field confocal optical coherence tomography (LC-OCT). Both methods revealed characteristic features such as hyperkeratosis, parakeratosis, acanthosis, nuclear pleomorphism of keratinocytes, and the presence of bright intraepithelial dendritic cells, correlating closely with histopathological findings of high-grade basaloid PeIN. Our findings highlight the valuable role of RCM and LC-OCT in improving the differential diagnosis of genital lesions, potentially reducing the need for invasive diagnostic procedures and ensuring early, appropriate management. Full article

Background/objectives: Despite advancements in early diagnosis and clinical practices guided by standardized care protocols, Merkel cell carcinoma (MCC) is marked by an unfavorable prognosis with a 5-year relative survival rate of 65%, based primarily on data collected prior to the introduction of immunotherapy. Regional nodal metastases affect 40–50% of MCC patients, while approximately 33% experience distant dissemination. Among these, bone and bone marrow metastases are particularly notable, although the characteristics and clinical implications of this metastatic disease in MCC remain poorly understood. Methods: A comprehensive review was conducted using the Medline database (via PubMed) up to January 2025. The search strategy included the string “(Merkel cell carcinoma AND (bone OR marrow))”. Results: A total of 1133 (69.3% male and 30.7% female) patients diagnosed with advanced MCC were collected. The median (IQR) age at diagnosis was 67.5 (12.65) years old. Overall, 201 (20.8%) cases of bone and/or bone marrow metastases were identified and linked to a primary known MCC in 75.7% of cases. Bone metastases (BMs) appear as the third most common metastatic site, following the liver (second) and lymph nodes (first). They show mixed biological and radiological behavior, with a marked preference for the axial skeleton over the appendicular one. Addressing the characteristics of metastatic bone disease, neurological symptoms were the most documented, whereas bone marrow involvement and leukemic spread seemed to be primarily related to immunosuppression. Multimodal treatment strategies, including platinum-based chemotherapy and radiotherapy, were the primary approaches adopted, reflecting therapeutic practices from the pre-immunotherapy era. Conclusions: The pattern of metastatic spread in MCC differs among studies, with the bones resulting as the third most common site of distant spread. Excluding head and neck MCC, which seems to be more regularly associated with liver metastases, the relationship between the primary tumor site and the development of bone or bone marrow metastases appears inconsistent. Overall, BMs mostly correlated with advanced MCC stages and poorer survival outcomes, with a median overall survival (OS) of 8 months (range 12.75–4). The integration of international guidelines, evolving evidence from clinical trials, and the expanding role of immune checkpoint inhibitors (ICIs) will contribute to improving systemic disease control and enhance patient care. Full article

Background: Although complete excision of suspicious melanocytic lesions is mandatory, it carries the risk of unnecessary scarring on one hand and inadequate treatment of misdiagnosed lesions on the other. Objectives: We evaluated the sensitivity, specificity, and predictive value of reflectance confocal microscopy (RCM) in diagnosing pigmented lesions with clinically ambiguous features―the so-called “gray zone” ―and compared its performance with the more established technique of epiluminescence microscopy (ELM). Results: Between 2019 and 2020, a total of 2282 melanocytic lesions were assessed using both ELM and RCM. Histopathological diagnosis aligned with the ELM risk classification in 91.6% of melanocytic lesions, specifically in 92.0% of very-high-risk lesions, 88.5% of high-risk lesions, 66.3% of medium-risk lesions, 96.3% of low-risk lesions, and 98.0% of very low-risk lesions. Similarly, histopathological diagnosis of these lesions corresponded with the RCM risk assessment in 91.2% of cases, including 90.9% of very-high-risk lesions, 84.4% of high-risk lesions, 93.1% of medium-risk lesions, 90.5% of low-risk lesions, and 96.2% of very low-risk lesions. Conclusions: Although ELM is a valuable tool for increasing the efficacy of clinical diagnosis, its reliability decreases for a group of lesions that appear suspicious during clinical skin examination. RCM, as a newer technique, appears to improve malignancy detection in suspicious melanocytic lesions without requiring excision; its sensitivity and specificity remain high even in lesions classified by ELM as posing a medium risk of malignancy. Full article

Background: Basal cell carcinoma (BCC) of the ocular and periocular region is characterized by a painless progressive extension. An early diagnosis can limit the extent of facial tissue involvement and subsequent resection resulting in better cosmetic and functional results. Objectives: The aim is to provide the largest and most up-to-date overview of ocular and periocular BCCs. We also reported the first case of caruncle BCC investigated by dermoscopy and reflectance confocal microscopy (RCM). Methods: A systematic review and meta-analysis (Prospero ID CRD583032) were carried out by searching PUBMED–MEDLINE, including all articles with a full-text English version and with BCCs in eyelids, medial and lateral canthus, caruncle, conjunctiva, and orbit. The following data were collected: authors, year, title and type of publication, medical specialization, number, sex, age and comorbidities of the patients, anatomic localization of the disease, clinical and dermoscopic aspect, histological examination, and treatment. Results: We identified 731 articles through a database search, of which 236 articles matched our inclusion criteria. A total of 71.730 patients with ocular and periocular BCCs were included in the present study, and all data collected were reported in a dataset. Most of the articles included were described by ophthalmologists (67.5%), dermatologists (11.2%), or plastic surgeons (5.6%). The proportional meta-analysis revealed varying significance and heterogeneity for each type of study included. Conclusions: BCC more frequently affects the lower eyelid. The most common BCC subtype of ocular and periocular area is the nodular form. Limited data are available concerning the application of dermoscopy and RCM in this area. RCM may be particularly useful for early diagnosis, mapping, and treatment monitoring of ocular and periocular BCCs. Surgery still remains the first-choice treatment. Full article

Background: Multiphoton tomography (MPT) is a femtosecond laser imaging technique that enables high-resolution virtual biopsies of human skin. It provides a non-invasive method for analyzing cellular metabolism, structural changes, and responses to cosmetic products, providing insights into cell–cosmetic interactions. This review explores the principles, historical development, and key applications of MPT in cosmetic research. Methods: The latest MPT device combines five modalities: (i) two-photon fluorescence: visualizes cells, elastin, and cosmetic ingredients; (ii) second harmonic generation (SHG): maps the collagen network; (iii) fluorescence lifetime imaging (FLIM): differentiates eumelanin from pheomelanin and evaluates the impact of cosmetics on cellular metabolic activity; (iv) reflectance confocal microscopy (RCM): images cell membranes and cosmetic particles; and (v) white LED imaging for dermoscopy. Results: MPT enables in-depth examination of extracellular matrix changes, cellular metabolism, and melanin production. It identifies skin responses to cosmetic products and tracks the intratissue distribution of sunscreen nanoparticles, nano- and microplastics, and other cosmetic components. Quantitative measurements, such as the elastin-to-collagen ratio, provide insights into anti-aging effects. Conclusions: MPT is a powerful in vivo imaging tool for the cosmetic industry. Its superior resolution and metabolic information facilitate the evaluation of product efficacy and support the development of personalized skincare solutions. Full article

Background/Objectives: The prevalence of tattoos has risen globally in recent decades, ranging from 10% to 29%. Although rare, melanomas arising within tattoos are challenging for dermatologists due to the complexities in clinical and dermoscopic evaluation. In this article, we report two cases of melanoma on tattoos, review the reported cases in the literature, and examine the role of reflectance confocal microscopy (RCM) in improving the diagnosis of melanoma on tattooed skin. Methods: We conducted a systematic literature search on Medline/Pubmed for the period from the inception of the databases to 31 October 2024, using the Mesh major topics ‘melanoma’ AND ‘tattoo’ OR ‘tattoo skin tumor’. Out of the 268 citations identified by our search, 37 studies met the eligibility criteria. Results: In total, 43 cases of melanoma arising on tattooed skin were identified, to which we add our 2 cases, bringing the total to 45. The most common locations were the upper limbs (53%) and trunk (38%), predominantly arisen on black and blue tattoos. Of 40 cases with known depth of invasion, 4 were in situ and 36 invasive, with a mean Breslow thickness of 2.7 mm. Seven patients had a positive sentinel lymph node. Of 16 cases with an available horizontal diameter, 12 melanomas had a diameter of ≥1 cm. Conclusions: The limited cases of ‘’melanoma on tattoos” reported in the literature suggest a coincidental association rather than a direct causal link. Nevertheless, increased awareness among patients and tattoo artists about potential risks and preventive measures may enhance the management of melanocytic lesions in tattooed individuals. Lastly, integrating reflectance confocal microscopy with dermoscopy increases the overall diagnostic accuracy for melanoma, enhancing the identification of pigmented and non-pigmented skin lesions. Full article

Background: Adult xanthogranulomatous disease (AXD) is a rare histiocytic disorder with systemic potential, while xanthelasma palpebrarum (XP) is a common xanthoma often linked to lipid disorders. Differentiating these conditions is challenging due to overlapping features. Reflectance confocal microscopy (RCM), a non-invasive imaging tool, offers high-resolution visualization of skin structures and may aid diagnosis. Methods: We present a 71-year-old woman with periocular lesions. RCM was used to evaluate the lesions, identifying cellular and structural features. The findings were confirmed through histopathology, followed by surgical excision. Postoperative monitoring utilized RCM and LC-OCT. Results: RCM identified Touton giant cells, foamy histiocytes, and fibrosis, helping to distinguish xanthogranuloma from xanthelasma. Histopathology confirmed the diagnosis, and the patient underwent successful lesion excision without complications. Conclusions: This case underscores RCM’s utility as a diagnostic adjunct for differentiating AXD from XP in sensitive regions like the periocular area. The combined use of RCM and LC-OCT enhances monitoring for recurrence. While histopathology remains the diagnostic gold standard, RCM shows promise as a non-invasive tool, warranting further research to validate its role and develop standardized clinical protocols. Full article

Early detection and comprehensive diagnostic approaches for breast cancer are essential for improving prognosis. When it comes to changes in the skin of the breast or the nipple–areola complex (NAC), particularly if they are unilateral, it is essential to be vigilant, as these changes could be an early sign of underlying malignancy or other pathologies. Primary breast malignancies, such as mammary Paget’s disease (MPD), can manifest as erythema, scaling, or ulceration of the NAC, while secondary cutaneous metastases from other breast carcinomas may present as nodules, erythematous plaques, or inflammatory reactions. Non-malignant inflammatory conditions, including eczema or mastitis, can also mimic these changes; histologic evaluation is the gold-standard diagnostic tool. The usefulness of conventional diagnostic techniques breast lesions has been confirmed, but in recent years, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) have emerged as additional tools to diagnose cases characterized by cutaneous changes; they may, therefore, result in new perspectives on the non-invasive diagnosis of MPD. RCM is a non-invasive diagnostic technique that allows high-resolution images of the skin at microscopic level in real time, offering a promising approach to the non-invasive diagnosis of MPD, particularly when a lesion is not clinically evident and may mimic other benign or inflammatory conditions. We describe an atypical clinical presentation of mammary Paget’s disease diagnosed early by reflectance confocal microscopy evaluation and confirmed histologically. Full article

Background/Objectives: Hidrocystomas, eccrine and apocrine, are rare cystic lesions that form benign tumors of the sweat glands. This study aimed to describe the clinical features of hidrocystomas and evaluate the role of non-invasive imaging techniques, including dermoscopy, Line-field Confocal Optical Coherence Tomography (LC-OCT), Reflectance Confocal Microscopy (RCM), and Ultra-High-Frequency Ultrasound (UHFUS), in their diagnosis. Methods: In total, seven cases of hidrocystomas were collected from the Dermatologic Clinic of the University of Siena, Italy. Predefined dermoscopic, LC-OCT, RCM, and UHFUS features were retrospectively described. Results: Overall, hidrocystomas were located on the face, mainly presenting as blue/purple-bluish translucent papules (71%). Dermoscopic examination revealed a homogeneous purple-bluish color (71%), white pale halo (71%), and shiny globules at the periphery (57%). LC-OCT identified a hyporeflective cupoliform round structure in the dermis with a bright and thick contour, while UHFUS showed a round structure in the dermis filled with hypoechoic content. Conclusions: Non-invasive imaging techniques could significantly enhance the diagnostic accuracy of hidrocystomas, aid in differentiation from other lesions, and minimize unnecessary biopsies. Full article

With the growing complexity of skin disorders and the challenges of traditional diagnostic methods, AI offers exciting new solutions that can enhance the accuracy and efficiency of dermatological assessments. Reflectance Confocal Microscopy (RCM) stands out as a non-invasive imaging technique that delivers detailed views of the skin at the cellular level, proving its immense value in dermatology. The manual analysis of RCM images, however, tends to be slow and inconsistent. By combining artificial intelligence (AI) with RCM, this approach introduces a transformative shift toward precise, data-driven dermatopathology, supporting more accurate patient stratification, tailored treatments, and enhanced dermatological care. Advancements in AI are set to revolutionize this process. This paper explores how AI, particularly Convolutional Neural Networks (CNNs), can enhance RCM image analysis, emphasizing machine learning (ML) and deep learning (DL) methods that improve diagnostic accuracy and efficiency. The discussion highlights AI’s role in identifying and classifying skin conditions, offering benefits such as a greater consistency and a reduced strain on healthcare professionals. Furthermore, the paper explores AI integration into dermatological practices, addressing current challenges and future possibilities. The synergy between AI and RCM holds the potential to significantly advance skin disease diagnosis, ultimately leading to better therapeutic personalization and comprehensive dermatological care. Full article

Background/Objectives: Facial pigmented skin lesions are extremely common, starting from the fourth to fifth decades, especially in South-European countries, often located in the periorbital region. These include malignant forms, Lentigo maligna (LM) and lentigo maligna melanoma (LMM), characterized by growing incidence, and a series of benign simulators, including solar lentigo (SL), pigmented actinic keratosis (PAK), seborrheic keratosis (SK) and lichen planus-like keratosis (LPK). The clinical differential diagnosis of atypical pigmented skin lesions (aPFLs) can be difficult, even for dermatologists, leading to inappropriate skin biopsies with consequent aesthetic impacts. Dermoscopy of the facial area is a specific dermoscopic field that requires dedicated training and proved to increase diagnostic accuracy in dermatologists. Since these lesions are often seen by ophthalmologists at first, we aimed to evaluate the effect of a focused dermoscopy training course on a group of ophthalmologists naïve to the use of a dermatoscope. Methods: A set of 80 periorbital pigmented skin lesions with both clinical and dermoscopic images was selected and evaluated by six ophthalmologists before and after a one-day intensive dermoscopic training course. They were required to evaluate 80 periorbital lesions one month before and after a one-day intensive dermoscopic training course, illustrating second-level diagnostic options such as reflectance confocal microscopy (RCM), obtaining a total of 480 evaluations. Specifically, they had to provide, for each case, a punctual diagnosis and a management option among dermoscopic follow-up/skin biopsy/RCM/LC-OCT. Descriptive statistics were carried out, and the accuracy (ACC), sensitivity (SE), and specificity (SP), with their 95% confidence interval (95% CI), were estimated. Results: In the pre-course test, ophthalmologists achieved 84.0% SP, 33.3% SE and 63.7% ACC, while after the course, SE increased by +9% (i.e., 41.7%), SP decreased by 4%, and ACC remained comparable, i.e., 64.6%. In the management study, the percentage of benign lesions for which a close dermoscopic follow-up was suggested significantly decreased (51.6% versus 22.2%), in parallel with an increase in the number of lesions referred for RCM. As for malignant cases, the reduction in responses “close dermoscopic follow-up” decreased from 37.0% to 9.9%, (−27%), in favor of RCM (+15%) and skin biopsy (+12%). Conclusions: The ophthalmologists proved to be very receptive in quickly metabolizing and putting into practice the concepts learned during the one-day intensive dermoscopy training course. Indeed, after only a one-day lesson, they were able to increase their SE by 9% and to improve their management strategy. The present findings highlight the importance of providing training ophthalmologists in dermoscopy during residency programs, in terms of benefits for the correct patient care. Full article

Background/Objectives: Primary cutaneous lymphomas (PCL) are a heterogeneous group of non-Hodgkin lymphomas arising from malignant T (CTCL) or B (CBCL) cells, often mimicking other skin conditions. Recently, non-invasive diagnostic imaging modalities, including dermoscopy, Reflectance Confocal Microscopy (RCM), and Line-field Optical Coherence Tomography (LC-OCT), have become increasingly important, supporting clinicians in clinical practice. Hence, our study aimed to describe dermoscopic, RCM, and LC-OCT features of PCL and to explore their role in PCL management. Methods: Between December 2022 and January 2024, 40 lesions of 25 patients with PCL were retrospectively analyzed at the Dermatologic Unit of the University of Siena, Italy. Predefined dermoscopic, LC-OCT, and RCM criteria were assessed and their frequencies were calculated. Results: At dermoscopy, CTCL lesions were characterized by pinkish structureless areas (58,6%) and homogeneous distributed dotted vessels (35,7%), whereas 57.1% of CBCL presented with orange-yellow structureless areas. Considering CTCL, lymphocytes in the epidermis, dermal-epidermal junction, and dermis were detected by LC-OCT in 73.1%, 66.7%, and 51.9% and by RCM in 72.2%, 55.6%, and 61.1% of cases, respectively. The detection of lymphocytes was more precise using RCM than LC-OCT in CTCL (p < 0.001). Dermal infiltration of medium-reflective cells was visible in 80% and 40% of CBCL cases by LC-OCT and RCM, respectively. Conclusions: Non-invasive imaging techniques may support clinicians in managing PCL; however, further studies are mandatory in this field. Full article

Background/Objectives: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine malignancy characterized by its propensity for rapid growth and early regional and distant metastasis. Given its potentially lethal nature, accurate and timely diagnosis of MCC is of utmost importance. This review aims to describe non-invasive imaging methods that can serve as additional tools in the examination of MCC. Methods: In this narrative review, we describe the up-to-date spectrum of non-invasive skin-imaging methods that can serve as additional tools in the examination of MCC based on the available literature. Dermoscopy might enhance the clinical diagnosis of MCC, facilitate differentiation from other benign and malignant tumors, and help optimize the treatment plan. New imaging technologies might also provide useful information at a sub-macroscopic level and support clinical diagnosis. These techniques include high-frequency ultrasound (HFUS), reflectance confocal microscopy (RCM) and optical coherence tomography (OCT). Results: Clinically, MCC typically presents as a rapidly growing, red, purple or skin-colored painless and firm nodule. Diagnosis is usually established with histopathological assessment and immunohistochemistry. However, dermoscopy and new imaging technologies might enhance the clinical diagnosis of MCC, facilitate differentiation from other benign and malignant tumors, and help optimize the treatment plan. Full article

Background: Traditional treatment methods for non-melanoma skin cancer (NMSC) include surgical excision with histological evaluation, yet advancements such as reflectance confocal microscopy (RCM) and superficial radiation therapy (SRT) offer non-invasive management alternatives. This study aims to evaluate the use of RCM for the evaluation of treatment outcomes after SRT in managing localized NMSC. Methods: A prospective interventional case series study was conducted on patients treated for NMSC with SRT between March 2020 and December 2023. Suspected NMSC lesions were initially evaluated with a handheld dermoscope and then imaged at multiple depths using a VivaScope 1500 RCM. Two dermatologists trained in RCM reviewed the images. Confirmed NMSC lesions were biopsied and treated with SRT, followed by RCM imaging at six months post-treatment to assess cancer clearance, scarring, and inflammation. Results: Of the 38 lesions (composed of SCC (24) and BCC (14)) treated affecting the 29 patients, all lesions showed no residual tumor activity upon conducting follow-up RCM (100% clearance). Scarring and mild erythema were noted clinically. Six lesions demonstrated moderate to severe inflammation at a 6-month follow-up. Conclusions: This study demonstrates successful non-invasive management of localized NMSC using RCM and SRT. RCM was able to non-invasively demonstrate complete tumor clearance achieved by SRT with minimal adverse effects. These findings support considering the use of RCM and SRT as primary diagnostic, monitoring, and treatment options for NMSC without the need for biopsies, especially for elderly patients or those unsuitable for surgery due to medical conditions. Full article