Fibroadenoma of the vulva with pseudoangiomatous stromal hyperplasia: A common neoplasm in uncommon site.

Mammary-type tissue in the vulva was first described in 1872 but has been rarely reported in the literature. This tissue was previously considered as ectopic breast tissue that occurs as a result of incomplete regression of the milk line. Similar to native breast tissue, ectopic mammary tissue is hormone-sensitive and can develop benign changes, such as fibroadenoma, as well as malignant changes. A more recent theory suggests that these benign and malignant mammary-type entities arise from mammary-like anogenital glands, which constitute normal vulvar components. We report a case of a 41-year-old woman who presented with a chronic asymptomatic cyst on the left vulva that eventually became uncomfortable, especially on standing. The cyst was located on the labium minus, measuring 1.0 × 0.5 cm, with no identified erythema or other skin abnormalities. Excision of the lesion and subsequent microscopic examination showed a circumscribed mass with a nodular overgrowth of epithelial and stromal components, resembling a mammary fibroadenoma with pseudoangiomatous stromal hyperplasia. We bring to attention this rare diagnosis and the importance of considering it in the presence of a vulvar lesion. The malignant and recurrence potential of mammary-type tissue necessitates excision with clear margins and close monitoring of these patients.

Treatment for central centrifugal cicatricial alopecia-Delphi consensus recommendations.

BACKGROUND: There is no established standard of care for treating central centrifugal cicatricial alopecia (CCCA), and treatment approaches vary widely. OBJECTIVE: To develop consensus statements regarding the use of various pharmacological therapies in treating adults with CCCA. METHODS: We invited 27 dermatologists with expertise in hair and scalp disorders to participate in a 3-round modified Delphi study between January and March 2023. Statements met strong consensus if 75% of respondents agreed or disagreed. Statements met moderate consensus if 55% or more but less than 75% agreed or disagreed. RESULTS: In round 1, 5 of 33 (15.2%) statements met strong consensus, followed by 9 of 28 (32.1%) in round 2. After the final round 3 meeting, strong consensus was reached for 20 of 70 (28.6%) overall statements. Two statements achieved moderate consensus. LIMITATIONS: This study included only English-speaking, US-based dermatologists and did not consider nonpharmacological therapies. CONCLUSION: Despite varying opinions among dermatologists, consensus was reached for several statements to help clinicians manage CCCA. We also highlight areas that lack expert consensus with the goal of advancing research and therapeutic options for CCCA.

Approach to the patient with hair loss.

Hair loss is a common complaint among both men and women and is associated with significant psychologic distress. Due to the varied causes, it is important to correctly diagnose the type of alopecia a patient is experiencing to ensure tailoring of treatment. This continuing medical education article describes the approach to diagnose alopecia based on current clinical practice and standards.

Development of the alopecia areata scale for clinical use: Results of an academic-industry collaborative effort.

BACKGROUND: The current classification for alopecia areata (AA) does not provide a consistent assessment of disease severity. OBJECTIVE: To develop an AA severity scale based on expert experience. METHODS: A modified Delphi process was utilized. An advisory group of 22 AA clinical experts from the United States was formed to develop this AA scale. Representatives from the pharmaceutical industry provided feedback during its development. RESULTS: Survey responses were used to draft severity criteria, aspiring to develop a simple scale that may be easily applied in clinical practice. A consensus vote was held to determine the final AA severity statement, with all AA experts agreeing to adopt the proposed scale. LIMITATIONS: The scale is a static assessment intended to be used in clinical practice and not clinical trials. CONCLUSION: The final AA disease severity scale, anchored in the extent of hair loss, captures key features commonly used by AA experts in clinical practice. This scale will better aid clinicians in appropriately assessing severity in patients with this common disease.

Preferentially expressed antigen in melanoma and p16 expression in acral melanocytic neoplasms.

Acral melanocytic neoplasms often pose diagnostic difficulty. Preferentially expressed antigen in melanoma (PRAME) expression and loss of p16 expression have diagnostic utility in melanocytic tumors. We examined PRAME and p16 expression in 30 acral melanocytic neoplasms (n = 11 nevi; n = 2 dysplastic nevi; n = 7 Spitz nevi; n = 10 acral melanomas). PRAME was scored as % positive nuclei: negative = 0%; 1% to 25% = 1+; 25% to 50% = 2+; 50% to 75% = 3+, or positive: 75% to 100% = 4+. p16 expression was defined as retained (homogeneous or checkerboard) or lost (complete or partial/regionally). PRAME expression was negative in all benign, dysplastic, and Spitz nevi. Conversely, all acral melanomas were diffusely (4+) positive for PRAME expression. p16 expression was retained in all benign acral nevi (8/11 homogeneous, 3/11 checkerboard), completely lost in one dysplastic nevus, and retained in all acral Spitz nevi (3/7 homogeneous, 4/7 checkerboard). p16 was retained in five of 10 acral melanomas (3/10 homogeneous; 2/10 checkerboard), and negative in five of 10 acral melanomas (absent in 3/10, partially lost in 2/10). Our data suggest that 4+ PRAME expression is highly sensitive and specific in the setting of acral melanomas and is a more predictive diagnostic tool compared with p16 immunohistochemistry.

A clinicopathologic analysis of 54 cases of cutaneous myxoma.

Cutaneous myxoma (CM) is an uncommon benign neoplasm of skin, which may be sporadic or arise in association with syndromes such as Carney complex. There has been only one large case series describing CM. We report 54 additional cases of CM; patients had a mean age of 55 years (range = 7-91), with a female-to-male ratio of 1.3. Most occurred on the trunk (n = 19), with the back being the most common site. The remainder presented on the lower extremity (n = 18), head and neck (n = 10), and arm (n = 7). Histopathologically, they were relatively circumscribed, nodular, and centered in the dermis. All had abundant myxoid stroma, a thin, arborizing vascular network, and spindled to stellate cells with no to mild atypia without mitotic activity. Follicular induction, stromal neutrophils, and intranuclear inclusions were present in 35%, 25%, and 61% of cases, respectively. Collagen trapping, splitting of collagen fibers, and encircling of hair follicles or eccrine glands were encountered in a subset. Thirty-nine cases were treated with shave excision, whereas 12 cases underwent wide local excision. Follow-up data were available for 28 of 54 cases (mean = 50 months). Only one case recurred at 36 months. This study suggests CM has a lower risk of local recurrence than previously reported.

Development and qualification of a machine learning algorithm for automated hair counting.

OBJECTIVE: Determining the amount of hair on the scalp has always been an important metric of patient satisfaction for hair growth and hair retention technologies. While simple in concept, this measurement is a difficult, resource intensive task for the dermatologist and the research scientist. Specifically, counting and measuring hair in phototrichogram images is very time consuming and labour intensive. Due to cost, often only a fraction of available images is manually analysed. There is a need for an automated method that can significantly increase speed and throughput while reducing the cost of counting and measuring hair in phototrichogram images. METHODS: Recent advances in machine learning and deep convolutional neural networks (deep learning) have led to a revolution in the analysis of image, video, speech, text and other sensor data. Image diagnostics have seen remarkable improvements with completely automated methods outperforming both human experts and human-engineered analysis methods. Deep learning methods can also provide speed and cost benefits. To enable use of a deep learning, we created a data set of 288 manually annotated phototrichogram images with marked location and length of each hair (the training dataset). We designed a custom neural network architecture and custom image processing algorithms to best utilize the available training data and to maximize performance for hair counting and length measurement. The performance of the algorithm was qualified by comparing hair count and length measurements to an independent ground truth method, the semi-manual Canfield's Hair Metrix method. RESULTS: Leveraging deep neural networks, we have developed capability to apply machine learning to reduce the time needed to acquire data from phototrichograms of patients' scalp from months to seconds. Our algorithm enables fast and fully automated hair counting and length measurement. The algorithm shows high agreement with human manually assisted analysis (ground truth). CONCLUSIONS: We have trained and deployed an algorithm utilizing this technology and have demonstrated the reproducibility, accuracy and speed of this algorithm that, once deployed, requires little to no recurring cost or manual intervention for its operation. The method allows fast analysis of large number of images, reducing study cost and significantly reducing study analysis time.

Scalp application of the antioxidant piroctone olamine reduces hair shedding in an 8-week randomized, double-blind, placebo-controlled clinical study.

OBJECTIVE: Increasing scalp hair fullness is a global unmet consumer need. An approach to decrease hair shedding by reducing scalp stratum corneum oxidation via a combination of antioxidant and barrier-enhancing technologies has been previously demonstrated. The purpose of this study was to test the effectiveness of the individual antioxidant piroctone olamine in two different product forms (shampoo or leave-on product) for activity to improve hair retention. METHODS: Female subjects with self-perceived hair thinning participated in an 8-week, double-blind, placebo-controlled, randomized clinical study to evaluate either a piroctone olamine (PO) containing shampoo or a PO containing leave on treatment, each relative to their corresponding placebo formulation Too many periods. Results for phototrichograms, TEWL, and biomarker analysis of scalp condition for the shampoo treatments are discussed. Phototrichogram results are shared for the assessment of the leave on treatment. RESULTS: Statistically significant increases in hair amount were observed by phototrichogram after use of both PO-containing products versus placebo formulations. The PO shampoo treatment also significantly decreased oxidative stress on the hair and scalp, and improved scalp condition as assessed by TEWL and scalp biomarker values. CONCLUSION: These results illustrate the effectiveness of a cosmetic antioxidant to improve scalp condition thereby improving hair retention. The observed improvements in scalp condition are consistent with previous reports with other antioxidant technologies and suggest that the hair retention effect was achieved by preventing oxidative damage to the scalp.

Scalp application of antioxidants improves scalp condition and reduces hair shedding in a 24-week randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: Increasing hair fullness is a global unmet need for many men and women. An approach to the problem is to decrease hair fall or shedding by reducing scalp stratum corneum oxidation and barrier damage to increase hair retention. This study evaluated a combination of functional antioxidants and barrier-enhancing cosmetic ingredients to improve scalp condition thereby enabling stronger hair anchorage and longer retention. METHODS: Male and female subjects with normal scalp condition and self-perceived hair thinning participated in a 24-week, double-blind, placebo-controlled, randomized clinical study assessing either a regimen of treatment shampoo and leave-on treatment containing functional antioxidant and barrier-enhancing agents or an identical placebo chassis shampoo control. The functional ingredients were piroctone olamine, zinc pyrithione, zinc carbonate, niacinamide, panthenol and caffeine. At baseline and after 8, 16 and 24 weeks of product use, several measurements were taken: hair shedding, total hair count (by phototrichogram), hair samples, TEWL and evaluation of biomarkers of scalp and hair conditions. Subjects also completed self-assessment questionnaires. RESULTS: Statistically significant effects for functional ingredient-containing treatment regimen versus a placebo control shampoo formulation were observed for reduced hair shedding, increased total hair count, reduced TEWL and improvement in scalp biomarker values. Subjects also noticed these improvements assessed via self-assessment questionnaires. CONCLUSIONS: These results establish that the use of functional antioxidant and barrier-enhancing agents to further improve scalp condition can enable a reduction in hair shedding and thus an increase in perceived hair fullness. The underlying improvements in scalp condition suggest the hair benefits were achieved as a result of improved scalp skin barrier and scalp condition leading to a viable preventative approach for hair thinning.

Disease Progression in Cutaneous Squamous Cell Carcinoma Patients With Satellitosis and In-transit Metastasis.

BACKGROUND/AIM: Satellitosis/in-transit metastasis (S-ITM) has prognostic value in melanoma and Merkel cell carcinoma, but is not incorporated into cutaneous squamous cell carcinoma (cSCC) staging. PATIENTS AND METHODS: From our IRB-approved registry, patients with high-risk cSCC, including patients with S-ITM, were identified. Univariate (UVA) and multivariate (MVA) analyses were performed to compare disease progression (DP) and overall survival (OS). Cumulative incidence of DP and OS analyses were performed using Fine-Gray and Kaplan-Meier methods, respectively. RESULTS: A total of 18 S-ITM subjects were compared to 247 high risk subjects including T3N0 (n=143), N1-N3 without extranodal extension (ENE) (n=56), N1-N3 with ENE (n=26) and M1 disease (n=22). Median follow up was 16.5 months. Three-year rates of DP were 22% for T3N0, 42% for S-ITM, 48% for T4 bone invasion, 50% for N1-N3 without extranodal extension (ENE), 53% for N1-N3 with ENE, and 66% for M1. Patients with S-ITM did not experience significantly worse DP compared to those with T3N0 (HR=1.96, 95%CI=0.8-4.9; p=0.14). CONCLUSION: Cutaneous SCC patients with S-ITM experienced outcomes similar to locally advanced non-metastatic cSCC patients. Larger studies are needed to guide incorporation into staging systems.

Vitamin D, autoimmunity and immune-related adverse events of immune checkpoint inhibitors.

In addition to its quintessential role in bone homeostasis, vitamin D also plays an important role in regulating the immune system. As such, many studies have demonstrated the therapeutic benefit of vitamin D in treating autoimmune diseases. This immunomodulatory activity of vitamin D has recently attracted more attention due to the rapid development of immunotherapies for cancers, including melanoma. Patients on cancer immunotherapies can suffer from immune-related adverse events (irAEs), which can involve any organ system and range from common dermatological reactions to extremely severe cases of fatal myocarditis in metastatic melanoma patients. Since there are currently no effective approaches to predict or prevent irAEs, it is attractive to potentially leverage the intriguing immunomodulatory effects of vitamin D within this context. This review will discuss recent research investigating the possibility of using vitamin D to alleviate autoimmunity and irAEs with the hope of improving outcomes for patients on cancer immunotherapies, especially within the context of dermatology.

Impact of clinical photographs on the accuracy and confidence in the histopathological diagnosis of mycosis fungoides.

BACKGROUND: The histopathological diagnosis of MF is challenging, and there is significant overlap with benign inflammatory processes. Clinical features may be relevant in the assessment of skin biopsies. METHODS: We provided photomicrographs to board-certified dermatopathologists and one hematopathologist with and without accompanying clinical photographs and assessed accuracy and confidence in diagnosing MF. RESULTS: We found that access to clinical photographs improved diagnostic accuracy in both MF and non-MF (distractors); the degree of improvement was significantly higher in the non-MF/distractor category. Across all categories, diagnostic confidence level was higher when clinical images were available. CONCLUSION: These findings suggest that clinical images are useful in making an accurate diagnosis of MF, and may be particularly helpful in ruling it out when an inflammatory disorder is clinically suspected.

Evaluating the Utility of Routine Imaging in Squamous Cell Carcinoma of the Nail Unit.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common malignant tumor of the nail unit. No guidelines currently exist regarding the role of imaging in this specific location. OBJECTIVE: To investigate the utility of routine imaging in SCC of the nail apparatus. METHODS: A multi-institutional retrospective review of patients treated for nail unit SCC was performed. Data were collected on patient characteristics, tumor qualities, treatment, and radiographic imaging. A change in treatment was defined as more aggressive treatment (amputation) rather than local excision or Mohs micrographic surgery (MMS). RESULTS: One hundred seven patients with nail unit SCC were identified. Approximately 44/107 (41.1%) of patients were imaged and 63/107 (58.9%) were not. Mohs micrographic surgery was the most common primary treatment (66.4%). Mohs micrographic surgery was more commonly performed in nonimaged patients, and amputation was more commonly performed in imaged patients (p < .001). Bony changes were identified in 13/44 (29.5%) of imaged patients. In 8/44 (18.2%), imaging findings caused a change in treatment. In 99/107 (92.5%) of the cohort, imaging was either not performed or did not change management. CONCLUSION: In select cases, imaging may help guide patient management. Sufficient evidence does not yet exist to support routine imaging for patients with nail unit SCC.

Diagnostic value of CD34 and calretinin immunostaining in the diagnosis of proliferating tricholemmal tumor and trichoblastoma.

BACKGROUND: Proliferating tricholemmal tumor (PTT) is a rare neoplasm of controversial biological behavior for which distinction from other more common tumors is essential. Similarly, trichoblastoma (TB) remains a debatable entity that may represent a variation of basal cell carcinoma (BCC). Our goal is to correlate the staining pattern of calretinin and CD34 in these two follicular tumors vs. their major differential diagnoses, invasive squamous cell carcinoma (ISCC) and BCC. METHOD: Descriptive study of 68 cases: 6 PTT, 22 TB, 20 ISCC, and 20 BCC in a period of 15 years. The diagnosis was confirmed with H&E. The immunohistochemistry results were analyzed and scored positive (weak +, moderate ++, and strong +++) or negative. RESULTS: Calretinin was expressed in 4/6 cases of PTT and negative in all TB. Only one malignant case of PTT was positive for CD34 (1/2) and negative in all TB cases. Calretinin and CD34 were negative for all ISCC and BCC. The intensities are shown in tables. CONCLUSION: The diagnosis of these neoplasms is a morphologic diagnosis. However, in those cases where the morphologic aspect is difficult to interpret, calretinin may assist in the diagnosis of PTT, distinguishing the hair follicle tumors with an outer root sheath differentiation. Likewise, CD34 showed significant affinity for the malignant subset of PTT. Calretinin and CD34 did not add any value to the differentiation between TB and BCC. However, this might suggest that both are the same entity with a different morphological permutation.