Identifying the potential origin of mucin in primary cutaneous mucinoses-A retrospective study and analysis using histopathology and multiplex fluorescence staining.

BACKGROUND: Primary cutaneous mucinoses (PCM) are rare diseases characterized by dermal or follicular mucin deposits. OBJECTIVES: A retrospective study characterizing PCM to compare dermal with follicular mucin to identify its potential origin on a single-cell level. MATERIAL AND METHODS: Patients diagnosed with PCM between 2010 and 2020 at our department were included in this study. Biopsy specimens were stained using conventional mucin stains (Alcian blue, PAS) and MUC1 immunohistochemical staining. Multiplex fluorescence staining (MFS) was used to investigate which cells were associated with MUC1 expression in select cases. RESULTS: Thirty-one patients with PCM were included, 14 with follicular mucinosis (FM), 8 with reticular erythematous mucinosis, 2 with scleredema, 6 with pretibial myxedema and one patient with lichen myxedematosus. In all 31 specimens, mucin stained positive for Alcian blue and negative for PAS. In FM, mucin deposition was exclusively found in hair follicles and sebaceous glands. None of the other entities showed mucin deposits in follicular epithelial structures. Using MFS, all cases showed CD4+ and CD8+ T cells, tissue histiocytes, fibroblasts and pan-cytokeratin+ cells. These cells expressed MUC1 at different intensities. MUC1 expression in tissue histiocytes, fibroblasts, CD4+ and CD8+ T cells, and follicular epithelial cells of FM was significantly higher than the same cell types in the dermal mucinoses (p < 0.001). CD8+ T cells were significantly more involved in expression of MUC1 than all other analysed cell types in FM. This finding was also significant in comparison with dermal mucinoses. CONCLUSION: Various cell types seem to contribute to mucin production in PCM. Using MFS, we showed that CD8+ T cells seem to be more involved in the production of mucin in FM than in dermal mucinoses, which could indicate that mucin in dermal and follicular epithelial mucinoses have different origins.

Agreement of dermatopathologists in the evaluation of clinically difficult melanocytic lesions: how golden is the 'gold standard'?

BACKGROUND: The 'gold standard' for the diagnosis of melanocytic lesions is dermatopathology. Although most of the diagnostic criteria are clearly defined, the interpretation of histopathology slides may be subject to interobserver variability. OBJECTIVES: The aim of this study was to determine the variability among dermatopathologists in the interpretation of clinically difficult melanocytic lesions. METHODS: This study used the database of MelaFind®, a computer-vision system for the diagnosis of melanoma. All lesions were surgically removed and sent for independent evaluation by four dermatopathologists. Agreement was calculated using kappa statistics. RESULTS: A total of 1,249 pigmented melanocytic lesions were included. There was a substantial agreement among expert dermatopathologists: two-category kappa was 0.80 (melanoma vs. non-melanoma) and three-category kappa was 0.62 (malignant vs. borderline vs. benign melanocytic lesions). The agreement was significantly greater for patients ≥40 years (three-category kappa = 0.67) than for younger patients (kappa = 0.49). In addition, the agreement was significantly lower for patients with atypical mole syndrome (AMS) (kappa = 0.31) than for patients without AMS (kappa = 0.76). LIMITATIONS: The data were limited by the inclusion/exclusion criteria of the MelaFind® study. This might represent a selection bias. The agreement was evaluated using kappa statistics. This is a standard method for evaluating agreement among pathologists, but might be considered controversial by some statisticians. CONCLUSIONS: Expert dermatopathologists have a high level of agreement when diagnosing clinically difficult melanocytic lesions. However, even among expert dermatopathologists, the current 'gold standard' is not perfect. Our results indicate that lesions from younger patients and patients with AMS may be more problematic for the dermatopathologists, suggesting that improved diagnostic criteria are needed for such patients.

Split-face study of melasma patients treated with non-ablative fractionated photothermolysis (1540 nm).

BACKGROUND: Melasma treatment remains challenging despite various laser systems available, because of potential side-effects and high recurrence rates. OBJECTIVE: Non-ablative fractionated photothermolysis (FP) is a promising therapeutic method, long-time results comparing treated vs. non-treated site are lacking. METHODS: A total of 14 patients were treated with FP in a split-face mode with standardized adjustments in three sessions (weeks 0, 3-4, 6-8, follow-up: 26-28). At each consultation, improvement was evaluated by patients and physicians. Objective assessment was performed using digital photographs and the pigment imaging tool SIAscope(®). RESULTS: Melasma improvement was registered in 83% and 75% of the cases 26-28 weeks after the first treatment based on two evaluations: by patient and by physician, respectively. Digital photography and SIAscope(®) revealed improvement in 54% and 85% after the first, 61% and 85% after the second, 41% and 58% after the third treatment, accordingly, mostly due to reduction of the outline sharpness. Patients with lighter skin complexions revealed significant improvement ranged from slight to moderate (P=0.03). Postinflammatory hyperpigmentation occurred in two cases with skin types III and IV. CONCLUSION: Non-ablative FP can be considered as a valuable treatment option with short-term improvement in terms of mild reduction and softening the edges of melasma in patients with skin types I/II, if prior topical therapies failed. Treatment of patients with skin types III+ should be critically questioned.

Diagnostic pitfall: pigmented lesion of the nipple--correlation between dermoscopy, reflectance confocal microscopy and histopathology.

We present an unusual case of a nevus of the nipple changing during pregnancy which caused a diagnostic pitfall. Nevi on the nipple and areola are infrequent, and diagnostic criteria for clinical, dermoscopy or reflectance confocal microscopy examination for nevi in this 'special location' are still missing. We comment on the literature on dermoscopic findings in mammary lesions and their management during pregnancy, as well as the challenging histopathology of nevi along the milk line. Finally, we focus on two main limitations of reflectance confocal microscopy: the misinterpretation of dendritic cells and the limitation of the imaging depth.

Dermoscopy patterns of nevi associated with melanoma.

It is well known that dermoscopy improves the diagnostic accuracy of pigmented skin lesions. Many dermoscopic criteria can be found both in nevi and in melanoma. For the correct interpretation of those criteria, formal training and clinical experience in dermoscopy is needed. This paper reviews the global and local dermoscopic features seen both in nevi and melanoma and focuses on the interpretation of those findings in order to differentiate between benign and malignant melanocytic skin tumors.

Dermoscopic features of melanomas associated with MC1R variants in Spanish CDKN2A mutation carriers.

BACKGROUND: The presence of at least one MC1R gene variant is associated with a reduction in age at melanoma diagnosis in families with CDKN2A mutations. OBJECTIVES: To describe dermoscopic features of early melanoma in CDKN2A gene mutation-positive Spanish individuals and to evaluate the possibility of a correlation between particular dermatoscopic pattern and MC1R gene variants. METHODS: Patients in whom a melanoma was diagnosed during specific follow up of high-risk individuals carrying CDKN2A mutations (with familial or personal history of previous melanoma) were included in this study. The decision to remove such melanomas was taken on the basis of history, clinical and dermoscopic evaluations including total body photography and digital dermoscopy. RESULTS: Of the nine patients included in this study, three were noncarriers of the red hair MC1R polymorphism, three patients had one red hair MC1R polymorphism and three patients had two red hair MC1R polymorphisms. On dermoscopic analysis of suspect melanocytic lesions we found that the mean +/- SD ABCD total dermoscopy score (TDS) was significantly higher in noncarriers of red hair MC1R polymorphisms than in carriers of two MC1R gene red hair variants (6.8 +/- 0.4 vs. 4.4 +/- 0.9; P = 0.014). CONCLUSIONS: Early melanomas in patients with two MC1R red hair variants may be difficult to diagnose definitively by dermoscopy because, in our limited experience, they show fewer colours and structures and have a lower TDS. In such melanomas, subtle atypical vessels and other changes detected by digital image follow up may be useful to confirm the diagnosis of melanoma. An integrated approach including clinical history and dermoscopic data (also considering additional information, such as the presence of atypical vessels) should be utilized in evaluating these high-risk patients. Further studies are necessary to confirm our suggestion.

Lichenoid Drug Eruption following Intravenous Application of Orally Formulated Diamorphine, a Semisynthetic Heroin.

BACKGROUND: Lichen planus is a common skin disorder of unknown etiology. Most cases are idiopathic, but substances such as gold, antimalarials, penicillamine, thiazide diuretics, ß-blockers, arsenic and nonsteroidal anti-inflammatory drugs have been implicated as trigger factors. CASE PRESENTATION: We report the case of a lichenoid eruption in a male drug addict who administered oral heroin (diamorphine) intravenously. Diamorphine was stopped immediately. Following topical steroids, phototherapy and oral acitretin, the lesions gradually disappeared. A lymphocyte transformation test was negative for pure morphine and codeine. DISCUSSION: A coincidental association between the intravenous application of orally formulated semisynthetic heroin and the lichenoid eruption cannot be completely ruled out. However, the diagnosis of a lichenoid drug eruption is favoured over idiopathic lichen planus because of the clear chronological correlation between drug use and appearance as well as drug withdrawal and disappearance of the skin lesions, and because of a flare-up following repeated intravenous application of diamorphine.

Subacute cutaneous lupus erythematosus triggered by radiotherapy.

BACKGROUND: The origin of collagen autoimmune diseases is not fully understood. Some studies postulate a mechanism of molecular mimicry or heterologous immunity following viral infections triggering autoimmunity. Apart from infections, other exogenous factors such as visible light or X-rays have been reported to incite autoimmunity. CASE REPORT: We report a case of histologically and serologically confirmed subacute lupus erythematosus (SCLE) following radiotherapy for breast cancer. DISCUSSION: The close temporal and spatial correlation between radiotherapy and onset of SCLE in this patient suggests that an autoimmune reaction may have been triggered locally by functionally altering the immune system and breaking self-tolerance.

Full-field optical coherence tomography for the rapid estimation of epidermal thickness: study of patients with diabetes mellitus type 1.

Changes in morphology of the skin are an important factor that can affect non-invasive measurements performed through this organ, in particular for glucose monitoring in e.g. patients with diabetes mellitus. A characterization technique for non-contact in vivo profiling of the superficial skin layers can be beneficial for evaluation of the performance of such measurement systems. We applied a full-field optical coherence tomography (OCT) system followed by the fully automatic processing for this task. With the developed procedure, non-invasive quantification of the skin morphology can be performed within a few minutes. The dorsal skin of the upper arm of 22 patients with Type 1 Diabetes Mellitus was investigated with an OCT system and with a commercially available dermatological laser scanning confocal microscope (CM) as a reference method. The estimates of epidermal thickness from OCT were compared with the results of expert-assisted analysis of confocal images. The highest correlation with the CM measurements has been obtained for the distance from the entrance peak to the first minimum of the OCT reflection profile (R2 = 0.657, p < 0.0001). In this specific patient group, we have observed a statistically significant correlation of the subjects' body mass index with the distance from the entrance peak to the dermal reflection peak in the OCT profile (p = 0.010). Furthermore, the same OCT parameter is negatively correlated with age with marginal statistical significance (p = 0.062). At the same time, no relation of diabetes-related parameters (duration of disease and concentration of glycated haemoglobin) to the skin morphology observed with the OCT and CM was found.

[Non-invasive techniques for the diagnosis of melanoma]. / Nicht-invasive Verfahren zur Diagnose des Melanoms.

In the last years a number of new non invasive techniques for the early diagnosis of melanoma have become very popular. In addition to dermoscopy, total body photography and digital dermoscopy frequently assist the dermatologist in differentiating nevi from early melanomas. A new promising technique for the non invasive diagnosis of melanoma might be confocal microscopy.

Dermoscopy in Gorlin-Goltz syndrome.

BACKGROUND: Gorlin-Goltz syndrome (GGS) is an autosomal dominant disorder mainly characterized by the presence of multiple basal cell carcinomas (BCC), odontogenic keratocysts of the jaw, and volar pits. This syndrome is associated with a wide spectrum of developmental anomalies and neoplasms. OBJECTIVE: To describe dermoscopic characteristics of cutaneous GGS lesions performing histopathologic correlation. MATERIALS AND METHODS: Cutaneous lesions and tumors from five patients affected by GGS were included. Clinical and dermoscopy images were obtained and excision with ulterior histopathology performed in suspicious tumors. RESULTS: With dermoscopy, BCCs can be detected in early stages by the presence of blue-gray globules in lesions less than 3 mm in diameter. In larger lesions, arborizing telangiectasia may also be present. Acral pits that are often overlooked during physical examination have a characteristic dermoscopy with red globules that are mainly distributed in parallel lines inside flesh-colored, irregular-shaped, and slightly depressed lesions. Dermoscopy improves the visualization of these pits. CONCLUSION: Dermoscopy can help in the diagnosis of the GGS as well as in the management of affected patients.