From endometrium to fingernail bed: histological evaluation of a rare cutaneous metastasis.

In the dermatological spectrum of oncologic manifestations, cutaneous metastases from endometrial carcinoma stand as a rarity, given the tumour's predilection for neighbouring uterine regions. We present an exceptional case of a patient in her mid-50s, whereby an endometrial carcinoma, defying conventional pathways, manifested on the skin and nail of her distal fourth finger, an unusual site for cutaneous metastases, with a specific histology of the primary cancer.

A History of Artificial Intelligence.

The development of the computer and what is now known as artificial intelligence (AI) has evolved over more than two centuries in a long series of steps. The date of the invention of the first computer is estimated at 1822, when Charles Babbage (1791-1871) developed his first design of a working computer on paper, based mainly on a Jacquard loom. He worked on his project together with Augusta Ada King, Countess Lovelace (née Byron) (Ada Lovelace) (1815-1852), whom he called the "Sorceress of Numbers." This work will present the profile and achievements of Charles Babbage, Augusta Ada King, Countess Lovelace, and Alan Mathison Turing (1912 - 1954), who is considered the father of computer science and artificial intelligence, and then provide an outline of the tumultuous events affecting AI up to the present.

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.

Editors and Journals: Part II-Relationship between the Editor-in-Chief and the Owner of the Journal: The Consequences When Editorial Independence Dissolves.

A symbiotic relationship between the editor and the owner of a medical journal is important for the journal to fulfill successfully the expectations of its readers and authors. Editorial freedom and transparency by owner of the journal are important qualities that enable the editor to provide valid scientific information in an unbiased manner. Unresolved impedance of editorial freedom or the persistent lack of transparency or both frequently results in untenable consequences for editor and often a substantial defamation of the journal's credibility. Unfortunately, misguided and inappropriate behavior by a medical society or the publication owner repeatedly occurs with the same devastating effect for the editor: prompt, unanticipated, and unjustified termination of the position at the journal. Alternatively, conditions imposed by a journal's owner may lead to the resignation of the editor because of untenable conditions. Because the owner does not have to account for its actions and there is no recourse for the editor, currently there seems to be no effective measures to prevent this tragic sequence of events in the future.

Editors and Journals: Part I-Responsibilities And Expectations Of Editors: Who Is the Editor and Why an Editor?

Important components of a medical journal include its readers, authors, editor, and owner. Editor is the individual to whom the journal is branded. The editor determines the journal's published content and establishes its caliber. The success of a journal depends on the general and specific responsibilities of the editor toward its readers, authors, and owner. For a journal to maintain its stature of excellence, the expectations of the editor-including editorial independence-must be preserved; therefore, in the best interest of the journal, the owner must provide unequivocal support to the editor.

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.

Dupilumab-associated mycosis fungoides: a cross-sectional study.

Treating atopic dermatitis (AD) with dupilumab, a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), may be associated with the progression of mycosis fungoides (MF).This study aims to examine the associations between the length of dupilumab treatment, age and sex, and the onset of MF.An institutional data registry and literature search were used for a retrospective cross-sectional study. Only patients with a diagnosis of MF on dupilumab for the treatment of AD and eczematous dermatitis were included.The primary outcome was the length of dupilumab exposure, age, sex, and the onset of MF. Linear correlations (Pearson) and Cox regression analysis were used to assess the correlation and the risk.A total of 25 patients were included in this study. Five eligible patients were identified at our institution. In addition, a PubMed review identified an additional 20 patients. At the time of MF diagnosis, the median age was 58, with 42% female. Disease history was significant for adult-onset AD in most patients (n = 17, 65.4%) or recent flare of AD previously in remission (n = 3, 11.5%). All patients were diagnosed with MF, and one patient progressed to Sézary syndrome while on dupilumab, with an average duration of 13.5 months of therapy prior to diagnosis. Tumor stage at diagnosis of MF was described in 19 of the cases and ranged from an early-stage disease (IA) to advanced disease (IV). Treatment strategies included narrow-band UVB therapy, topical corticosteroids, brentuximab, pralatrexate, and acitretin. Male gender, advanced-stage disease, and older age correlated significantly with the hazard of MF onset and a shorter time to onset during dupilumab treatment.Our results suggest a correlation between the duration of dupilumab treatment and the diagnosis of MF, the higher MF stage at diagnosis, and the shorter the duration of using dupilumab to MF onset. Furthermore, elderly male patients appeared to be more at risk as both male gender and older age correlated with a hazard of MF diagnosis. The results raise the question as to whether the patients had MF misdiagnosed as AD that was unmasked by dupilumab or if MF truly is an adverse effect of treatment with dupilumab. Close monitoring of these patients and further investigation of the relationship between dupilumab and MF can shed more light on this question .

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.

To treat or not to treat: PD-L1 inhibitor-induced keratoacanthoma and squamous cell carcinoma.

Keratoacanthoma (KA) and squamous cell carcinoma (SCC) are rare side effects of programmed cell death ligand-1 (PD-L1) inhibitors that can disrupt therapy. There is no consensus on optimal treatment. We investigated the management strategy and factors influencing pathophysiology. An institutional cancer registry and literature search were used for this retrospective study. Only PD-L1-induced KA and SCC cases were included. Pathology specimens were stained with immune markers and management strategies were analyzed. Four cases were identified at our institution. Immunohistochemistry of atypical keratinocytes revealed PD-1/PD-L1 positivity, high p53, and low bcl-2 for all cases with differential expression of CD44 and beta-catenin for KA versus SCC. Nivolumab was continued or temporarily held with complete resolution. In addition, a literature search identified 30 additional cases of KA/SCC after PDL-1 inhibitor use. The most common treatment was excision/destruction followed by topical and/or intralesional corticosteroids. Therapy was definitely withheld in 22% of KA patients and in 9% of SCC cases. The expression of PD-L1 by atypical keratinocytes helps to explain the effects of nivolumab on the development of cutaneous neoplasms. The expression of immune markers provides mechanistic insights into pathophysiology. Management may be achieved with conservative therapy and without treatment interruption.

Case Presentation: Monkeypox.

Monkeypox is a rare viral disease that initially appeared in West and Central Africa, and is primarily transmitted to humans from animals. It moved to the United States in 2003, which was the first time the disease had left the African continent. It is still uncommon in the United States and elsewhere, although outbreaks have occurred, especially in gay communities,1-3 causing it to be declared a health emergency in some areas. (SKINmed. 2022;20:410-411).

Limitations of randomized, controlled, double-blinded studies in determining safety and effectiveness of treatments.

Randomized, controlled, double-blinded studies, in which treated subjects are randomly selected from the same pool as controlled (untreated) ones and neither the caregiver nor the patient knows which is which, are widely accepted as the gold standard of experimental medicine. There are well-documented advantages of such studies. There are, however, significant limitations of them as well of which it is important to be aware. Notably, physicians who rely on experience and on what they were taught in medical school and post-graduate training are not necessarily wrong when this information runs contrary to the results of such studies. Some limitations of them are widely known and taught, such as inadequate sample size, failure of proper randomization, et cetera; others are less well-known. We shall focus on the latter.

The impact of diabetes mellitus on medical complication and mortality rates among inpatients with bullous pemphigoid.

BACKGROUND: There is currently limited population-based data on the effect of type 2 diabetes mellitus (T2DM) on bullous pemphigoid (BP) inpatients. AIMS: To evaluate the relative comorbidities, medical complications, and mortality rates between BP inpatients with and without T2DM. METHODS: All inpatients with a primary BP diagnosis in the National Inpatient Sample from 2003 to 2012 were queried. BP inpatients with or without T2DM were compared to identify disparities in relative comorbidities and medical complications. Comorbidities were established using the Agency for Healthcare Research and Quality standardized values. Medical complications were classified using ICD-9 codes. RESULTS: Of the 1978 BP patients identified, 660 (33.4%) had a concurrent diagnosis of T2DM. These patients had significantly higher rates of concurrent comorbidities, including chronic renal failure, congestive heart failure, iron deficiency anemia, hypertension, obesity, and peripheral vascular disease. On bivariate analysis, T2DM patients also had significantly higher rates of medical complications including acute kidney injury (14.5% vs. 10.1%, p = 0.004) and venous thromboembolism (1.8% vs. 0.5%, p = 0.012). On multivariable-adjusted analysis, the odds of venous thromboembolism (OR = 3.01, p = 0.027) remained increased. Inpatient mortality did not differ between the groups. CONCLUSIONS: Our findings suggest that BP inpatients with T2DM have a greater medical comorbidity and complication burden. However, inpatient mortality was not increased.