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Background: Melanoma disease patterns vary with patient age., Aim: To evaluate sentinel lymph node biopsy (SLNB) in managing melanoma at differing patient ages., Methods: Online prediction tools were applied to compare SLNB positivity (SLNB + ) and survival risk at patient ages 20-80. Tübingen melanoma data were used to determine variations in the hazard ratio of SLNB + for mortality at different patient ages., Results: Regardless of tumour thickness, predicted SLNB + rates were markedly higher than mortality rates for 20-year-old patients. For 80-year-old patients, it is the opposite., Discussion: If 1000 20-year-olds with a 0.4 mm thickness non-ulcerated melanoma underwent SLNB, 100 would likely be positive. If all 100 were to be offered adjuvant drug therapy (ADT), fewer than three more melanoma deaths in those 1000 patients would be avoided. In total, 97 patients would have received medication they may never have needed. If 1000 80-year-olds with a 3 mm thickness non-ulcerated melanoma underwent SLNB, only 40 would likely be positive. In total, 274 patients would be predicted to die of melanoma, 245 being SLNB negative and 29 SLNB + . ADT linked to SLNB + could deny treatment to 89% of these high-risk patients., Limitations: The authors relied on published risk data., Conclusion: SLNB has poor specificity at predicting mortality in young melanoma patients and poor sensitivity in older patients. SLNB is not indicated in managing cutaneous melanoma for patients under 40 or over 60 years of age. Many such patients could be managed with wide local excision alone in their clinician's office-based practice. For all cutaneous melanoma patients at all ages, linking ADT to BAUSSS biomarker, (an algorithm of Breslow thickness, age, ulceration, subtype, sex and Site) rather than SLNB + is likely more appropriate. BAUSSS provides a more accurate melanoma-specific mortality risk assessment for patients without burdening them with added surgery, hospitalization, costs or morbidity risk., (© 2024 European Academy of Dermatology and Venereology.)

Over the past few years, high-resolution optical imaging technologies such as optical coherence tomography (OCT), reflectance confocal microscopy (RCM), and multiphoton microscopy (MPM) have advanced significantly as new methodologies for clinical research and for real-time detection, diagnosis, and therapy monitoring of skin diseases. Implementation of these technologies into clinical research and practice requires clinicians to have an understanding of their capabilities, benefits, and limitations. This concise review provides insights on the application of OCT, RCM, and MPM for clinical skin imaging through images acquired in vivo from the same lesions. The presented data are limited to pigmented lesions and basal cell carcinoma., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Multiphoton microscopy (MPM) is a promising non-invasive imaging tool for discriminating benign nevi from melanoma. In this study, we establish a MPM morphologic catalogue of common nevi, information that will be critical in devising strategies to distinguish them from nevi that are evolving to melanoma that may present with more subtle signs of malignancy. Thirty common melanocytic nevi were imaged in vivo using MPM. Quantitative parameters that can distinguish between different types of nevi were developed and confirmed by examining the histology of eleven of the imaged nevi. MPM features of nevi examined included cytologic morphology of melanocytes in the epidermis and dermis, the size and distribution of nevomelanocytes both within and around nests, the size of rete ridges, and the presence of immune cells in the dermis. Distinguishing features include cytological morphology, the size of nevomelanocytes, the size of nevomelanocyte nests, and the distribution of nevomelanocytes. Notably, these distinguishing characteristics were not easily appreciated in fixed tissues, highlighting essential differences in the morphology of live skin. Taken together, this work provides a morphologic compendium of normal nevi, information that will be critical in future studies directed at identifying melanocytic nevi that are evolving to melanoma., (© 2020 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

The treatment of cutaneous squamous cell carcinoma in situ by Mohs micrographic surgery is currently deemed as appropriate by the Mohs Appropriate Use Criteria. However, squamous cell carcinoma in situ is a very superficial, indolent, low-risk tumor amenable to destructive and non-surgical treatments. It is uncommon for squamous cell carcinoma in situ to have progressed to invasive malignancy subsequent to definitive management. The suggestion that squamous cell carcinoma in situ on certain anatomic locations has a poorer prognosis is widely assumed but lacks an evidence base. We recommend that most primary squamous cell carcinoma in situ in non-immunosuppressed patients be scored inappropriate or uncertain for Mohs micrographic surgery by the Mohs Appropriate Use Criteria. Multiple other efficacious treatment options exist for managing squamous cell carcinoma in situ, including curettage and cryotherapy, curettage and electrodessication, and topical therapies.

Angiokeratomas can present therapeutic challenges, especially in cases of extensive lesions, where traditional surgical methods carry high risks of scarring and hemorrhage. Argon, pulsed dye (PDL), neodymium-doped yttrium aluminum garnet (Nd:YAG), copper vapor, potassium titanyl phosphate, carbon dioxide, and erbium-doped yttrium aluminum garnet (Er:YAG) lasers have emerged as alternative options. To review the use and efficacy of lasers in treating angiokeratomas. A PubMed search identified randomized clinical trials, cohort studies, case series, and case reports involving laser treatment of cutaneous angiokeratomas. Twenty-five studies were included. Quality ratings were assigned using the Oxford Centre for Evidence-Based Medicine scheme. Several laser modalities are effective in treating multiple variants of angiokeratomas. Vascular lasers like PDL, Nd:YAG, and argon are the most studied and of these, PDL offers the safest side effect profile. Nd:YAG may be more effective for hyperkeratotic angiokeratomas. Combination treatment with multiple laser modalities has also demonstrated some success. Lasers are a promising treatment option for angiokeratomas, but current use is limited by the lack of treatment guidelines. There are limited high quality studies comparing laser treatments to each other and to non-laser options. Additional studies are needed to establish guidelines and to optimize laser parameters., (© 2017 Wiley Periodicals, Inc.)

Importance: Basal cell carcinomas (BCCs) are diagnosed by clinical evaluation, which can include dermoscopic evaluation, biopsy, and histopathologic examination. Recent translation of multiphoton microscopy (MPM) to clinical practice raises the possibility of noninvasive, label-free in vivo imaging of BCCs that could reduce the time from consultation to treatment., Objectives: To demonstrate the capability of MPM to image in vivo BCC lesions in human skin, and to evaluate if histopathologic criteria can be identified in MPM images., Design, Setting, and Participants: Imaging in patients with BCC was performed at the University of California-Irvine Health Beckman Laser Institute & Medical Clinic, Irvine, between September 2012 and April 2014, with a clinical MPM-based tomograph. Ten BCC lesions were imaged in vivo in 9 patients prior to biopsy. The MPM images were compared with histopathologic findings., Main Outcomes and Measures: MPM imaging identified in vivo and noninvasively the main histopathologic feature of BCC lesions: nests of basaloid cells showing palisading in the peripheral cell layer at the dermoepidermal junction and/or in the dermis., Results: The main MPM feature associated with the BCC lesions involved nests of basaloid cells present in the papillary and reticular dermis. This feature correlated well with histopathologic examination. Other MPM features included elongated tumor cells in the epidermis aligned in 1 direction and parallel collagen and elastin bundles surrounding the tumors., Conclusions and Relevance: This study demonstrates, in a limited patient population, that noninvasive in vivo MPM imaging can provide label-free contrast that reveals several characteristic features of BCC lesions. Future studies are needed to validate the technique and correlate MPM performance with histopathologic examination.

Background and Significance: There is a need to develop non-invasive diagnostic tools to achieve early and accurate detection of skin cancer in a non-surgical manner. In this study, we evaluate the capability of stimulated Raman scattering (SRS) microscopy, a potentially non-invasive optical imaging technique, for identifying the pathological features of s squamous cell carcinoma (SCC) tissue., Study Design: We studied ex vivo SCC and healthy skin tissues using SRS microscopy, and compared the SRS contrast with the contrast obtained in reflectance confocal microscopy (RCM) and standard histology., Results and Conclusion: SRS images obtained at the carbon-hydrogen stretching vibration at 2945 cm(-1) exhibit contrast related protein density that clearly delineates the cell nucleus from the cell cytoplasm. The morphological features of SCC tumor seen in the SRS images show excellent correlation with the diagnostic features identified by histological examination. Additionally, SRS exhibits enhanced cellular contrast in comparison to that seen in confocal microscopy. In conclusion, SRS represents an attractive approach for generating protein density maps with contrast that closely resembles histopathological contrast of SCC in human skin., (© 2013 Wiley Periodicals, Inc.)

Background: Placental site trophoblastic tumor (PSTT) is a rare neoplasm of intermediate trophoblastic cells of the placenta. There is a wide range of biologic behavior, with metastases occurring in about 15% of cases. Cases with metastases have all presented with abnormal vaginal bleeding or gynecological symptoms., Methods: We describe a 31-year-old G3P3003 woman who presented with several alopecic patches resembling alopecia areata, which on biopsy proved to be metastatic, previously unsuspected, PSTT., Conclusions: This represents the first case in which PSTT presented initially with metastases, and specifically, with cutaneous metastases. A new primary tumor source of alopecia neoplastica is presented. The role of mitotic counts in predicting prognosis in PSTT is supported. Alopecia areata was mimicked very closely. Dermatologists should be alert to any features atypical of alopecia areata, including erythema, induration, or palpability, and maintain a low threshold for biopsy in atypical cases.

Background: Anti-human epithelial antigen (Dako-Ber-EP4) is an antibody raised in mice that reacts with two glycoproteins of 34 and 49 kD. These glycoproteins are present on the cell surface and in the cytoplasm of basal cell carcinoma (BCC) cells, sweat glands, and some hair follicles in the skin., Methods: We selected 27 BCCs (15 nodular, 11 morpheic/infiltrative, and one adenoid) and one trichoblastoma and performed rapid immunohistochemical studies with Ber-EP4 and a labeled streptavidin biotin alkaline phosphatase system., Results: Twenty-seven of 27 BCCs and one of one trichoblastoma were positive for Ber-EP4. Thirteen of 27 BCCs stained with Ber-EP4 showed areas of BCC in dense inflammation that were better defined by the Ber-EP4 immunostain than by the H&E stain. In two cases persistent infiltrative BCC was found in the final Mohs margins while appearing negative with routine H&E. Several instances occurred where negative Ber-EP4 in inflammatory fields resulted in tissue sparing with the avoidance of a further Mohs (insurance) layer., Conclusion: In conclusion, we found mouse anti-human Ber-EP4 a useful and reliable marker for BCC. This antibody helps to locate latent BCC tumor in inflammatory Mohs margins.

Background and Design: In this study we developed an in vitro model of nodular basal cell carcinoma (BCC). We obtained pure cultures of BCC cells and compared the morphologic characteristics, ultrastructure, immunophenotype, and behavior of cultured tumor cells with those of their in vivo counterparts. Tumors were excised from patients undergoing Mohs micrographic surgery. We established 69 primary cell cultures from 32 patients with nodular BCC., Results: Three cell types grew in primary cultures: fibroblasts, normal-appearing keratinocytes, and cells with dual (spindle and epithelioid) morphologic characteristics. Contaminating fibroblasts were removed using 0.125% trypsin-0.02% edetic acid, and normal-appearing keratinocytes were cornified and eliminated by temporarily increasing the concentration of calcium in the growth medium. The cells with dual morphologic characteristics remained intact and exhibited relentless growth in pure cultures. That these seemingly immortal cell strains represent true nodular BCC was demonstrated by (1) their biphasic morphologic characteristics and very slow cell growth rate, (2) their capability for anchorage-independent growth in soft agar, (3) their ultrastructural similarities to freshly excised nodular BCC, (4) their ability to generate antibodies selectively labeling nodular BCC tumor nests in vivo, and (5) their immunophenotypic similarities to BCC in vivo on more than 20 different cell markers., Conclusions: This study provides a simple technique for establishing pure cell cultures of nodular BCC and describes extensively the in vitro parameters of tumor cell growth. The striking differences in behavior of cultured tumor cells in the presence or absence of normal-appearing keratinocytes suggest that normal human epidermal keratinocytes can suppress the growth of BCC cells.

Background: Recurrence of squamous cell carcinoma (SCC) following Mohs micrographic surgery is uncommon. However, such cases do exist, presumably because of incomplete excision. Identification of single cells or small clumps of SCC tumor may be extremely difficult and can be compromised by inflammatory reaction., Objective: The purpose of this study was to evaluate the benefits of incorporating rapid cytokeratin (CK) stains into Mohs technique., Methods: Simple modification of standard immunoenzyme techniques allows keratin-specific staining to be achieved in less than 90 minutes on Mohs cryostat sections. We used the rapid labeled streptavidin biotin anticytokeratin method at the stage when no tumor was apparent by hematoxylin and eosin staining in 20 patients with large, aggressive, or recurrent invasive SCCs., Results: In eight cases, single cells or small clumps of SCC tumor were identified utilizing AE-1 monoclonal antibody. These patients subsequently underwent further surgery, including wider tumor resection, superficial parotidectomy, or postoperative radiation therapy., Conclusion: The rapid CK antibody staining technique enhances the sensitivity of tumor identification in Mohs micrographic surgery, and should reduce tumor recurrence rates.

In the routine handling of Mohs specimens the curetted first layer is integral to the process of tumor identification. Small specimens may be smeared inadvertently on filter paper or gauze or even lost between the operating room and laboratory. An efficient method for processing small curetted specimens has been devised that bypasses the use of a tissue tray. This method improves tissue morphology and saves time.

We have studied eight cases of an acquired lymphatic endothelial lesion for which we propose the name "benign lymphangioendothelioma." The lesions developed as solitary, slowly extending, erythematous macules and plaques, usually occurring on the extremities or the shoulders in adolescents or adults. The characteristic histopathologic feature is permeation of the dermal collagen by flattened, endothelium-lined channels and spaces. Hemorrhage, iron deposition, and inflammation were not part of the lesion. Ulex europaeus agglutinin I labeled the lesional endothelial cells consistently, but factor VIII-related antigen labeling was negative. This histologic pattern and the special studies suggested a lymphatic lesion. Surgical excision, performed in six patients, was not followed by recurrence.

Rhinophyma, the end stage in the development of rosacea, is characterized by sebaceous hyperplasia, fibrosis, follicular plugging and telangiectasia. Although it is commonly considered a cosmetic problem, it can result in gross distortion of soft tissue and in airway obstruction. Previously, basal-cell carcinoma (BCC) has been reported in association with rhinophyma. We are reporting an additional case in which the patient had been delaying treatment because of the 'cosmetic nature' of this condition.

Precise identification and localization of tumor is the key to success in Mohs micrographic surgery. In a pilot study, we demonstrated improvement in tumor definition and staining characteristics after formalin fixation of cryostat sections (postfixation) when compared with unfixed specimens. We further investigated the benefits of postfixation with a series of tissue fixatives and with varying fixation times. In all cases, postfixation was found to be beneficial. No improvement was noted by extending the postfixation time beyond 1 minute.