Novel B-DNA dermatophyte assay for demonstration of canonical DNA in dermatophytes: Histopathologic characterization by artificial intelligence.

We describe a novel assay and artificial intelligence-driven histopathologic approach identifying dermatophytes in human skin tissue sections (ie, B-DNA dermatophyte assay) and demonstrate, for the first time, the presence of dermatophytes in tissue using immunohistochemistry to detect canonical right-handed double-stranded (ds) B-DNA. Immunohistochemistry was performed using anti-ds-B-DNA monoclonal antibodies with formalin-fixed paraffin-embedded tissues to determine the presence of dermatophytes. The B-DNA assay resulted in a more accurate identification of dermatophytes, nuclear morphology, dimensions, and gene expression of dermatophytes (ie, optical density values) than periodic acid-Schiff (PAS), Grocott methenamine silver (GMS), or hematoxylin and eosin (H&E) stains. The novel assay guided by artificial intelligence allowed for efficient identification of different types of dermatophytes (eg, hyphae, microconidia, macroconidia, and arthroconidia). Using the B-DNA dermatophyte assay as a clinical tool for diagnosing dermatophytes is an alternative to PAS, GMS, and H&E as a fast and inexpensive way to accurately detect dermatophytosis and reduce the number of false negatives. Our assay resulted in superior identification, sensitivity, life cycle stages, and morphology compared to H&E, PAS, and GMS stains. This method detects a specific structural marker (ie, ds-B-DNA), which can assist with diagnosis of dermatophytes. It represents a significant advantage over methods currently in use.

Artificial intelligence and the scientific method: How to cope with a complete oxymoron.

Artificial intelligence (AI) can be a powerful tool for data analysis, but it can also mislead investigators, due in part to a fundamental difference between classic data analysis and data analysis using AI. A more or less limited data set is analyzed in classic data analysis, and a hypothesis is generated. That hypothesis is then tested using a separate data set, and the data are examined again. The premise is either accepted or rejected with a value p, indicating that any difference observed is due merely to chance. By contrast, a new hypothesis is generated in AI as each datum is added to the data set. We explore this discrepancy and suggest means to overcome it.

Xeroderma Pigmentosum: Novel Prophylactic and Therapeutic Approaches. Part One: Topical Zinc Sulfate 25% and Heat Dermabrasion plus Topical Trichloroacetic Acid.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease; relatively mild XP patients are sometimes designated as having pigmented xerodermoid or xerodermoid pigmentosum (XP-V), a variant of XP. It is commonly associated with many long-standing skin conditions and tumors, including malignancies, management of which is necessary to prevent the progress of the disease. The objective of the study was to report the use of a number of innovative therapeutic and prophylactic treatments, beyond surgery, such as topical 5-fluorouracil, topical imiquimod, other topical immunomodulators, or photodynamic therapy, in treating skin eruptions and their complications in XP patients. This was a prospective therapeutic interventional study in which 50 patients with XP-V were evaluated. Age of subjects ranged from 2 to 50 years with a mean age of 18 years. This study was divided into two parts. In part one, patients were treated by applying topical zinc sulfate 25% twice daily on entire face for 2 months, then once daily for several months or years. In another instance, two women were treated with heat dermabrasion with needle diathermy on the entire face under local anesthesia, followed by application of trichloroacetic acid 35% peeling in a single session. In part two, topical podophyllin 25% was used as therapy for 18 patients, all of whom had XP complications, such as keratoacanthoma, basal cell carcinomas and squamous cell cancers.1 Podophyllin was applied to the lesions until complete resolution was documented. All patients treated with topical zinc sulfate 25% responded well as determined by clearance of actinic keratoses (ActK) and small malignant lesions, minimization of pigmented freckles, prevention of new lesions, and ceased progress of eruptions. Heat dermabrasion administered in a single session resulted in the clearance of pigmented freckles, ActK, and small tumors, and cessation of new eruptions during follow-up that continued for up to 6 years.

Xeroderma Pigmentosum: Part Two: Treatment of Skin Tumors with Topical Podophyllin 25% in Benzoin.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease; relatively mild XP patients are sometimes designated as having pigmented xerodermoid or xerodermoid pigmentosum (XP-V), a variant of XP. It is commonly associated with many long-standing skin conditions and tumors, including malignancies, management of which is necessary to prevent the progress of the disease. The objective of the study was to evaluate an innovative therapeutic treatment, beyond surgery, surgical excision, cryotherapy, electrocautery and curettage, or Mohs surgery, for the management of skin tumors in XP.This was a prospective therapeutic interventional study comprising 50 patients with XP-V. Age of subjects ranged from 2 to 50 years, with a mean age of 18 years. Several measures were evaluated in part one of this study, and a number of others (as reviewed in part one) were successful in prophylaxis of skin tumors in XP as well as in treating earlier stigmata of XP; however, these measures were notably less successful in treating well-developed skin tumors in XP patients, and 18 of the 50 patients evaluated in part one had well-developed tumors (total 22 lesions) refractory to treatments. Podophyllin 25% in 100-mL tincture of benzoin was applied topically to lesions until complete resolution was documented in 18 patients with XP complications, such as keratoacanthoma (KA), basal cell carcinoma, or squamous cell carcinoma. Topical podophyllin 25% in benzoin was a less destructive alternative treatment for skin cancer and KA in XP patients.

Annular and acral/facial dyskeratotic paraneoplastic disorders.

Annular and acral/facial dyskeratotic paraneoplastic disorders are inflammatory dermatoses that occur in association with distant cancers but are not precursors, extensions, or metastases of them. There are four classical entities under this rubric: two gyrate entities, erythema annulare centrifugum and erythema gyratum repens, and two acral/facial dyskeratotic entities, acrokeratosis paraneoplastic (Bazex syndrome) and tripe palms. Each of these entities may also occur in association with another etiopathogenesis and may present either as a classical entity or as a barely recognizable disease. We discuss these entities, their associated causes, and their differential diagnoses in turn.

Occult squamous cell carcinoma within lichenoid dermatitis: three examples of cryptic cancer detection.

Lichenoid dermatitis can be a perplexing entity encompassing an array of cutaneous disorders. Two hundred forty-three (243) cases of otherwise unclassifiable lichenoid dermatitis were examined histologically employing a special cytokeratin stain. Occult squamous cell carcinoma was detected in three of the 243 cases, uncovered by special immunohistochemistry staining within histologic specimens of lichenoid dermatitis. We recommend staining for cutaneous cancer becoming a routine practice in evaluating cutaneous lichenoid dermatitis.

What we have learned from the COVID-19 pandemic: Time to think outside the box, maybe far outside.

The coronavirus disease 2019 pandemic has had a profound effect on our lives and careers; this presentation explores some of the lessons we have learned from it and others that it may yet teach us. Socioeconomic effects have been profound, not all of them favorable. Travel and meeting activities, as well as many other activities, have been severely restricted. Social unrest has become intense, and it may have questionable political consequences, as the United States is undergoing a contested election result.

The pathophysiology of pityriasis alba: Time-dependent histologic changes.

Although pityriasis alba is a common dermatologic condition, its pathogenesis is poorly understood, and there are many discrepancies in the literature. To assess the effect of the duration of disease on the histologic findings, a search of cases labeled "pityriasis alba" was performed on any cases submitted to our dermatopathology laboratory. Of 179 cases of pityriasis alba, five cases identified the duration of the disease, when the biopsy was taken. A biopsy for a lesion of only 1-month duration demonstrated groups of large, prominent melanocytes heaped up upon one another. Compared with biopsies from patients who had the lesions for increasingly longer periods of time, it was apparent that the melanocytes became progressively less abundant and smaller with less prominent dendritic processes. The time that the biopsy is taken may affect the histologic findings of pityriasis alba. Additionally, an abundance of melanosomes was observed between the melanocytes in all sections examined which may reflect a problem with the transfer of melanosomes into keratinocytes in this condition.

The physiology of melanin deposition in health and disease.

Eumelanin is the major pigment responsible for human skin color. This black/brown pigment is localized in membrane-bound organelles (melanosomes) found in specialized cells (melanocytes) in the basal layer of the epidermis. This review highlights the steps involved in melanogenesis in the epidermis and the disorders in skin pigmentation that occur when specific steps critical for this process are defective. Melanosomes, which contain tyrosinase, a major enzyme involved in melanin synthesis, develop through a series of steps in the melanocyte. They are donated from the melanocyte dendrites to the surrounding keratinocytes in the epidermis. In the keratinocytes, the melanosomes are found singly or packaged into groups, and as the keratinocytes move upward in the epidermis, the melanosomes start to degrade. This sequence of events is critical for melanin pigmentation in the skin and can be influenced by genetic, hormonal, and environmental factors, which all play a role in levels of melanization of the epidermis. The effects these factors have on skin pigmentation can be due to different underlying mechanisms involved in the melanization process leading to either hypo- or hyperpigmentary disorders. These disorders highlight the importance of mechanistic studies on the specific steps involved in the melanization process.