In Vivo Histological Study Evaluating Non-Ablative Fractional 1940-nm Laser.

OBJECTIVES: Non-ablative fractional lasers (NAFL) have increased in demand compared to ablative laser treatments as they provide lesser down time, fewer side-effects, and are safer to use. Non-ablative fractional treatment with lasers ranging from 1320 to 1927-nm have been shown to be safe and effective for skin resurfacing procedures. The objective of this study is to investigate healing of the 1940-nm NAFL-induced microthermal treatment zones (MTZs) in human skin from a histologic perspective. METHODS: Three subjects received 1940-nm NAFL treatment to test areas on the abdomen at various timepoints during the study. The minimum 5 mJ/MTZ and maximum 20 mJ/MTZ energy settings were used at 20% coverage. Biopsies were taken coinciding with immediately posttreatment, 1, 3, 7 days, and 6 weeks posttreatment. Blinded analysis of hematoxylin and eosin stained slides was performed to measure the width and depth of the MTZs and evaluate the inflammatory and healing response of the skin over time (immediately to 6 weeks posttreatment). Safety was evaluated by assessing local skin responses and adverse events immediately after treatment and at all study visits. RESULTS: Histological analysis of tissue following NAFL 1940-nm treatments showed mild early inflammatory response (presence of lymphotic infiltrate) in some test areas and zones of necrosis and coagulation having widths and depths (immediately-3 days posttreatment) that scaled with the 1940-nm pulse energy. Signs of healing such as presence of dermal mucin, evidence of fibrosis, and absence of necrosis were observed long-term (7 days to 6 weeks posttreatment). Evidence of the MTZ persisted beyond the 6-week study and was predicted to last for 100 days. All local clinical skin responses healed within 6 weeks and were limited to mild, transient erythema and edema which resolved in less than 12-24 h following treatment. No serious adverse events occurred during the study. CONCLUSIONS: NAFL 1940-nm treatments are safe for inducing small fractional coagulation and necrosis zones in abdominal skin. NAFL 1940-nm laser creates fractional columns of injury with sufficient depth and coverage that suggest effective skin resurfacing, like other non-ablative fractional lasers.

Optimizing Dermatological Care Triage in a Safety-Net Hospital: Retrospective Analysis of Diagnoses and In-Person Referrals.

OBJECTIVES: Teledermatology is a cost-effective and efficient approach to delivering care and is particularly beneficial for patients with limited access to specialized services. Considering the rapid expansion of telehealth, it is crucial to focus on optimization. The purpose of our study was to evaluate the triaging of dermatologic care in an electronic consultation (e-consultation) service in a safety-net hospital. METHODS: This was a 2-year retrospective review of a dermatology asynchronous store-and-forward e-consultation service. RESULTS: A total of 1425 patients completed 1502 e-consultation. Of these e-consultations, 46% of the patients had Medicaid and 44% were Black or African American. The top three diagnoses were dermatitis unspecified, neoplasm of uncertain behavior, and acne/rosacea. Most (68%) were managed via e-consultation and did not require an in-person appointment. Children and adolescents were more likely to require an in-person appointment (74%) compared with adults (30%, P < 0.0001). Patients with a chief complaint of hair loss or skin lesion were more likely to require in-person evaluation (58% and 41%, respectively) compared with rash (24%) and acne (18%) (P < 0.0001). There was no difference found in recommendations for in-person evaluation based on race, non-English-language preference, or insurance status. CONCLUSIONS: E-consultation services seem well suited for certain concerns, and underserved populations can be evaluated by teledermatology.

Melanocytic hyperplasia associated with surgical scars in basal cell carcinoma re-excision specimens: A single-center retrospective study.

BACKGROUND: Melanocytic hyperplasia (MH) overlying surgical scars has been reported but MH adjacent to the scar has not been previously addressed. METHODS: We evaluated scar-associated MH in 489 re-excision specimens of basal cell carcinoma. Melanocytic density, confluence, atypia, suprabasal scatter, follicular extension, distance from the scar, correlation with clinicopathologic parameters, and PRAME expression were recorded. RESULTS: One hundred seventy-seven of 489 (36%) cases exhibited MH beyond the scar extending to 6.65 mm median distance, with a median density of 13 melanocytes/0.5 mm (6-24 mm), confluence in 74 (42%) cases, atypia in 14 (8%), suprabasal melanocytes in 25 (14%), and follicular extension in 21 (12%). Mean age of MH group was significantly lower than non-MH group (P < 0.0001). MH overlying the scar was significantly higher in specimens with elastosis than those without elastosis (P < 0.0001). PRAME expression was absent in 14 of 20 cases and present in rare melanocytes in 6 cases. CONCLUSIONS: Increased melanocytic density with confluence, mild atypia, suprabasal scatter, and superficial follicular extension may be observed in re-excision specimens adjacent to surgical scars in the absence of a melanocytic neoplasm. These observations are helpful for appropriate interpretation of melanoma re-excision specimens, to avoid potential pitfalls in diagnosis and unnecessary therapeutic measures.

Treatment of facial and non-facial lentigines with a 730 nm picosecond titanium: Sapphire laser is safe and effective.

OBJECTIVE: A 730 nm picosecond-domain laser was developed to improve the clearance of pigmented lesion and reduce adverse events. This study assessed the safety and efficacy of this system for the clearance of lentigines and explores how the short picosecond pulses interact with tissue via histology. STUDY DESIGN AND METHODS: Twenty subjects with Fitzpatrick skin types II-IV were enrolled in this prospective, IRB-approved study. Four treatments were administered using a 730 nm picosecond-domain laser. Pre- and posttreatment photos were assessed by blinded reviewers at 4- and 12-week follow-up visits, using a 5-point clearance scale. Subject satisfaction was measured using a 5-point scale. Investigator Global Improvement Score (IGIS) was performed at the 4- and 12-week follow-up visits, using an 11-point clearance scale. Subject pain level was measured using an 11-point scale (no pain [0], extreme pain [10]). Histology of 730 and 532 nm picosecond pulses was compared with 755 and 532 nm nanosecond pulses. RESULTS: Sixteen subjects with a total of 118 discontinuous treatment areas, each comprised of 1-20 lesions, completed all study visits. Thirty body regions were studied, including arms (6), hands (16), scalp (1), forehead (2), face (3), and back (2). Spot sizes ranging from 2 to 5 mm diameters were used with fluences ranging from 0.8 to 4.0 J/cm2 . Mean pain score was 3.6 of 10 for all four treatments. Ninety-nine percent of randomly paired 4-week posttreatment images and 100% of 12-week posttreatment images were correctly identified from their respective baseline images by three blinded reviewers. Mean IGIS demonstrated scores of 6.7 and 7.0 at 4- and 12-week follow-up visits, respectively. At the 4- and 12-week follow-up visits, 76% and 73% of subjects, respectively, were satisfied to highly satisfied. The mean clearance score for all 118 treatment areas was 3 of 4 in follow-up visits. At 12-week follow-up, 36% of 118 treatment areas had a clearance score of 4, and 38% had a clearance score of 3. Post treatment, there was typical erythema, edema, dryness, crusting, and itching but negligible purpura, no pinpoint bleeding, blistering or scarring, and no significant hyperpigmentation or hypopigmentation. Histology showed diffuse, focal epidermal vacuolization ~5-10 µm in diameter and mild extravasation of erythrocytes with 730 nm picosecond pulses, while diffuse epidermal vacuolization was observed with coalescence of vacuoles (~20-100 µm), junctional clefting and mild extravasation of erythrocytes with 755 nm nanosecond pulses. Picosecond pulses of the wavelength of 532 nm produced diffuse, focal epidermal vacuolization and larger dermal vacuoles to depths of 500 µm, while 532 nm nanosecond pulses produced diffuse epidermal vacuolization with coalescence of vacuoles and marked dermal hemorrhage. CONCLUSION: This study demonstrated the potential of a new 730 nm picosecond-domain laser for the clearance of lentigines. The results showed good clearance with no adverse events and good subject satisfaction in patients with skin type II-III. Additional studies need to be conducted on darker skin types. The histopathologic findings demonstrate that the picosecond 730 nm laser produces excellent selectivity for pigment with minimal disruption of the dermal-epidermal junction and may therefore reduce healing times and the risk of adverse events.

Baby Wet Wipes: An Unusual Culprit of Lymphomatoid Contact Dermatitis Mimicking Mycosis Fungoides.

ABSTRACT: Lymphomatoid contact dermatitis (LCD) is a rare, benign pseudolymphoma with clinicopathologic features of both allergic contact dermatitis and cutaneous T-cell lymphoma (CTCL). In this article, we report a fascinating case of LCD secondary to chronic baby wet wipe use with clinical features of allergic contact dermatitis and histopathologic changes of mycosis fungoides, a subtype of CTCL. We argue that LCD should be added to the list of mimickers of mycosis fungoides, a subtype of CTCL.

Diagnostic Value of Plasmacytoid Dendritic Cells in Differentiating Pityriasis Lichenoides et Varioliformis Acuta From Lymphomatoid Papulosis.

ABSTRACT: Pityriasis lichenoides et varioliformis acuta (PLEVA) and lymphomatoid papulosis (LyP) can often demonstrate clinical and histopathologic overlap. A recent study demonstrated significant plasmacytoid dendritic cell (pDC) recruitment in lesions of PLEVA, whereas another study reported minimal pDC recruitment in lesions of LyP. To confirm the possible diagnostic value of pDCs in differentiating PLEVA and LyP, we compared the presence and distribution of pDCs and myxovirus protein A (MxA) expression (an indirect assessment of pDC activity). In total, 19 cases of PLEVA (16 patients) and 14 cases of LyP (11 patients) were examined using immunohistochemical stains for anti-blood-derived dendritic cell antigen-2 and MxA. Individual semiquantitative scoring systems were used to assess the immunohistochemical results, and a Mann-Whitney test with a subsequent 2-tailed P test was performed for statistical analysis. No statistically significant difference in the number of pDCs in both groups was found. However, most PLEVA cases (84%) demonstrated intense and diffuse MxA expression, whereas LyP cases (71%) demonstrated weak patchy staining (P < 0.007). Our study suggests that although additional studies may be needed to determine whether pDCs are more relevant to the pathogenesis of PLEVA or LyP, pDC activity through MxA staining may play a role in differentiating PLEVA from LyP and may serve as a platform for additional studies.

Merkel Cell Carcinoma In Situ: No More Serendipity?

ABSTRACT: A 50-year-old man, with a history of extensive sun exposure and multiple previous non-melanoma skin cancers, presented with an asymptomatic 8-× 10-millimeter scaly, skin-colored papule on his right shoulder. Subsequent biopsy and excision revealed epidermal hyperplasia containing large atypical basaloid cells with pagetoid spread. Immunoperoxidase staining for cytokeratin-20 demonstrated a focal perinuclear dot-like pattern, and after excluding other in situ entities, a diagnosis of Merkel cell carcinoma In Situ (MCCIS) was rendered. MCCIS is a very rare entity. Although approximately 18% of Merkel cell carcinomas have epidermal involvement, currently only 17 cases of MCCIS have been reported, of which only 7 had no associated neoplasm. Previously, MCCIS was considered a serendipitous or incidental finding, as most cases co-existed with squamous cell carcinoma in situ. This case is unique in that it was not associated with a squamous lesion, and in addition, the pagetoid spread was unusual and has only occasionally been described. As such, MCCIS should be added to list of in situ epidermal lesions with pagetoid spread.

Histopathological Changes Induced by Malassezin: A Novel Natural Microbiome Indole for Treatment of Facial Hyperpigmentation.

BACKGROUND: Malassezin is a natural indole compound produced by the fungus Malassezia furfur and preclinical investigations have demonstrated an ability to suppress melanogenesis. OBJECTIVE: To investigate the histopathological effects of malassezin for treatment of facial hyperpigmentation. METHODS: In this proof-of-concept study, seven subjects with facial hyperpigmentation caused by melasma or photodamage applied topical malassezin twice daily for 14 weeks, followed by eight weeks of observation. At baseline, 2 mm punch biopsies were taken from hyperpigmented areas and adjacent uninvolved skin. Skin biopsies from hyperpigmented areas were repeated at 8, 14, and 22 weeks. Paraffin-embedded sections were cut and stained with H&E, Fontana Masson, and MART 1 and assessed for histopathological changes. RESULTS: Increased epidermal melanin and dermal melanophages were observed in all biopsies at baseline in the hyperpigmented compared to uninvolved skin of all subjects. Eight and 14 week biopsies of involved skin revealed decreased epidermal melanin in all subjects treated with malassezin. Melanocytes appeared less dendritic compared to baseline, and numbers were slightly reduced at eight weeks. Biopsies at 22 weeks showed no significant difference in epidermal melanin levels compared to baseline hyperpigmented skin, and melanocytes were comparable in number and dendricity to baseline. There was no evidence of melanocyte atypia in any of the biopsies. These features were similar in melasma and photo-damaged skin. CONCLUSION: This study documents the histopathological features and ability of malassezin, a novel agent unique to the skin microbiome, to decrease epidermal pigmentation and the temporary and revisable nature of the process. J Drugs Dermatol. 2022;21(2):141-145. doi:10.36849/JDD.6596.

Perivascular Adventitial Fibroblast Specialization Accompanies T Cell Retention in the Inflamed Human Dermis.

Perivascular accumulation of lymphocytes can be a prominent histopathologic feature of various human inflammatory skin diseases. Select examples include systemic sclerosis, spongiotic dermatitis, and cutaneous lupus. Although a large body of work has described various aspects of the endothelial and vascular smooth muscle layers in these diseases, the outer adventitial compartment is poorly explored. The goal of the current study was to characterize perivascular adventitial fibroblast states in inflammatory human skin diseases and relate these states to perivascular lymphocyte accumulation. In normal skin, adventitial fibroblasts are distinguished by CD90 expression, and dense perivascular lymphocytic infiltrates are uncommon. In systemic sclerosis, this compartment expands, but lymphocyte infiltrates remain sparse. In contrast, perivascular adventitial fibroblast expression of VCAM1 is upregulated in spongiotic dermatitis and lupus and is associated with a dense perivascular T cell infiltrate. VCAM1 expression marks transitioned fibroblasts that show some resemblance to the reticular stromal cells in secondary lymphoid organs. Expanded adventitial compartments with perivascular infiltrates similar to the human settings were not seen in the inflamed murine dermis. This species difference may hinder the dissection of aspects of perivascular adventitial pathology. The altered perivascular adventitial compartment and its associated reticular network form a niche for lymphocytes and appear to be fundamental in the development of an inflammatory pattern.

Osteoclast-Like Giant Cells: Focus on Entities Relevant to Dermatopathology and Underlying Pathogenesis.

ABSTRACT: Osteoclast-like giant cells (OLGCs) resemble osteoclasts with their abundant cytoplasm and well-developed organelles. OLGCs are characteristic features of giant cell tumor of the tendon sheath and giant cell tumor of soft tissue but they have also been described in numerous other cutaneous conditions. The diagnostic and prognostic significance of the presence of OLGCs is unknown. Here, we summarize the clinical entities that can exhibit these cells to avoid a histological overlap, affecting diagnosis and management.

Differences Between Recommended Surgical Margins and Measured Histological Margins in Malignant Melanoma In Situ and Malignant Melanomas.

ABSTRACT: Wide local excision (WLE) using appropriate surgical margins is the standard surgical management for malignant melanoma in situ (MMIS) and primary cutaneous malignant melanoma (MM). The actual width of the histologic margins is frequently not assessed, whereas narrow histologic margins are associated with an increase in local melanoma recurrence. Our objective was to analyze the actual measured histological margins of WLE specimens of MMIS and MM cases and compare them with their recommended surgical margins. A retrospective study of formalin fixed specimens of MMIS and invasive MM treated with WLE from a large university-affiliated dermatopathology laboratory was conducted. Among a total of 164 MMIS and 128 MM cases, 14 MMIS (8.5%) and 7 MM (5.9%) had positive lateral margins. The median histologic margin for MMIS, after a 15% tissue shrinkage adjusted, was 2.7 mm [1.3-3.9] for LM type and 3.9 mm [2.3-5.6] for non-LM type, in contrast to the recommended 5-mm margin. In 96 MM of T1 type (≤1.0 mm), the median adjusted histologic margin was 6.7 mm [3.5-9.1] in contrast to the recommended 10-mm margin. These results show that measured and adjusted median histologic margins in WLE specimens in both MMIS and MM of T1 type were significantly narrower than the recommended surgical margins, regardless of anatomic location. These differences are concerning, whether they reflect clinicians' intentional or unintentional deviation from recommended guidelines.

Neuroendocrine Differentiation of Skin Tumors: A Comprehensive Review.

Neuroendocrine differentiation is characterized by endocrine and neuronal features with prominent dense secretory granules and neuropeptides. Neuroendocrine differentiation of skin tumors is of unknown clinical significance. Nonetheless, the acknowledgment of this line of differentiation is important to prevent diagnostic pitfalls and subsequent inappropriate management. This review aims at summarizing the skin neoplasms that can express neuroendocrine markers.

Extensive CD34-to-CD90 Fibroblast Transition Defines Regions of Cutaneous Reparative, Hypertrophic, and Keloidal Scarring.

BACKGROUND: CD90 fibroblasts have been described arising from and replacing the homeostatic CD34 network in scleroderma, but have not been specifically examined in other forms of cutaneous fibrosis. OBJECTIVES: To address expression, timelines, and spatial relationships of CD90, CD34, and smooth muscle actin (SMA) expressing fibroblasts in scars and to examine for the presence of a CD34-to-CD90 transition. METHODS: One hundred and seventeen scars (reparative/hypertrophic/keloidal) were evaluated for CD90, CD34, and SMA expression. Double-staining immunohistochemistry for CD90/CD34 was performed to identify CD90/CD34 transitioning cells, confirmed by double-color immunofluorescence. In addition, some scars were double-stained with CD90/SMA, CD90/procollagen-1, or SMA/procollagen-1 to evaluate spatial relationships and active collagen synthesis. Expression was graded as diffuse, minority, and negative. RESULTS: Most scars demonstrate a CD90/CD34 pattern, and dual CD90/CD34 fibroblasts were observed in 91% of scars. In reparative scars, CD90 expression reverses to a CD34/CD90 state with maturation. Pathologic scars exhibit prolonged CD90 expression. Both CD90 and SMA fibroblasts collagenize scars, although CD90 fibroblasts are more prevalent. CONCLUSIONS: CD90 fibroblasts likely arise from the resting CD34 fibroblastic network. Actively collagenizing scar fibroblasts exhibit a CD90/CD34 phenotype, which is prolonged in pathologic scars. CD90 fibroblasts are likely important players in cutaneous scarring.

Primary Cutaneous Spindle Cell Squamous Carcinoma Expressing Smooth Muscle Actin: Diagnostic Pitfalls.

Alpha smooth muscle actin (SMA) belongs to the actin proteins. It is a known immunohistochemical marker for tumors of mesenchymal origin. There have been reports of expression of SMA in certain epithelial malignancies in the head and neck and genital regions. In this study, the authors report a primary cutaneous spindle cell squamous carcinoma expressing SMA. Both high- and low-molecular-weight keratins and p63 were positive, and S100 protein, SOX10, MART-1/Melan-A, and muscle-specific actin stains were negative. This case highlights that an epithelial tumor could express a mesenchymal marker, thereby making the diagnosis problematic.

Epidermotropic cutaneous metastases of squamous cell carcinoma from primary esophageal cancer: report of a case and review of the literature.

Metastatic squamous cell carcinoma (SCC) to the skin can be distinguished histologically from primary cutaneous squamous cell carcinoma as, unlike the latter, it is typically separated from the normal overlying squamous epithelium. Rare cases have been reported of cutaneous metastases of SCC that demonstrate continuity with the overlying benign squamous epithelium, termed "epidermotropic cutaneous metastases of SCC." We report the first case of epidermotropic cutaneous metastases of SCC originating from primary esophageal SCC with a review of the literature on this rare histological phenomenon.

Syringocystadenoma papilliferum on the mons pubis.

It is relatively rare to find syringocystadenoma papilliferum (SCAP) outside the head and neck region and extremely rare in the anogenital area. Characteristic histological features such as cystic invaginations, glandular epithelium showing decapitation secretion, and stroma with plasma cells are important for making the diagnosis. We present a rare case of SCAP on the mons pubis of a 13-year-old girl and compare cases of SCAP from other rare locations.

Altered Dermal Fibroblasts in Systemic Sclerosis Display Podoplanin and CD90.

Tissue injury triggers the activation and differentiation of multiple cell types to minimize damage and initiate repair processes. In systemic sclerosis, these repair processes appear to run unchecked, leading to aberrant remodeling and fibrosis of the skin and multiple internal organs, yet the fundamental pathological defect remains unknown. We describe herein a transition wherein the abundant CD34(+) dermal fibroblasts present in healthy human skin disappear in the skin of systemic sclerosis patients, and CD34(-), podoplanin(+), and CD90(+) fibroblasts appear. This transition is limited to the upper dermis in several inflammatory skin diseases, yet in systemic sclerosis, it can occur in all regions of the dermis. In vitro, primary dermal fibroblasts readily express podoplanin in response to the inflammatory stimuli tumor necrosis factor and IL-1ß. Furthermore, we show that on acute skin injury in both human and murine settings, this transition occurs quickly, consistent with a response to inflammatory signaling. Transitioned fibroblasts partially resemble the cells that form the reticular networks in organized lymphoid tissues, potentially linking two areas of fibroblast research. These results allow for the visualization and quantification of a basic stage of fibroblast differentiation in inflammatory and fibrotic diseases in the skin.

Cutaneous involvement in luteinized thecomas with sclerosing peritonitis (LTSP)-A new finding in a rare syndrome.

Luteinized thecomas with sclerosing peritonitis (LTSP) is a rare disease characterized by ovarian luteinized thecomas and associated fibrosing peritonitis. Cutaneous involvement has never been reported. We report a case of classical LTSP with skin involvement, outlining the clinical and histopathologic features of this novel presentation of a rare syndrome.

Benign and malignant hybrid adnexal tumors in a patient with epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is a genodermatosis characterized by overgrowth of flat warts, pityriasis versicolor-like lesions and an increased propensity for developing cutaneous squamous cell carcinomas due to abnormal susceptibility to infection with beta-human papilloma viruses. Adnexal tumors are not typically associated with EV. Here we report a spectrum of hybrid adnexal tumors with divergent eccrine and folliculosebaceous differentiation, and cytologic features ranging from benign to frankly atypical, in a patient with inherited EV.