Mpox virus and coinfections: An approach to rapid diagnosis.

We report a case of a 42-year-old immunocompromised (human immunodeficiency virus [HIV], CD4 count 86 cells/µL) Black male who presented with fever, oropharyngeal candidiasis, and phimosis, followed by eruption of umbilicated papulovesicles most concentrated on the face. The patient was diagnosed with Mpox (MPXV, formerly monkeypox), herpes simplex virus 1 (HSV1), varicella-zoster virus (VZV), and late latent syphilis. Tzanck smear of a Mpox lesion proved a useful and rapidly obtained pertinent negative test, lacking the typical changes of HSV/VZV (multinucleation, margination, and molding). A biopsy specimen showed viral changes consistent with both Mpox (ballooning degeneration and multinucleated keratinocytes) and herpesvirus (multinucleated epithelial giant cell within a zone of follicular necrosis). Lesion PCR was positive for HSV1 and MPXV, and negative for HSV2 and VZV. Immunohistochemistry was positive for VZV and orthopoxvirus. Empiric treatment for HSV/VZV in patients with suspected or confirmed Mpox should be considered for patients with HIV or other immunocompromised patients. It is important to recognize that MPXV, HSV, and VZV may all be present and difficult to distinguish clinically. More than one test modality (PCR, H&E, immunohistochemistry, and Tzanck) and multiple lesion samples may be required to thoroughly evaluate widespread papulovesicular eruptions, especially in immunocompromised patients.

Peculiar vegetative tumor-like genital herpes simplex nodules with brisk tissue eosinophilia in patients with human immunodeficiency virus infection.

Genital herpes simplex virus (HSV) infection in a human immunodeficiency virus (HIV) patient can present as a vegetative nodule. Clinical differential diagnoses of the nodule include condyloma latum, condyloma acuminatum, viral or fungal infection, and cutaneous neoplasms. Histological examination of herpetic nodules has been reported to show thick pseudoepitheliomatous hyperplasia with dense dermal lymphoplasmacytic infiltrate and multifocal multinucleated cells with herpetic viral cytopathic changes. We report two patients with HIV presenting with vegetative tumor-like HSV nodules with distinctive histopathologic pattern of inflammation that has not been described in the literature before. All samples displayed slightly acanthotic epidermis with focal ulceration, dense dermal sclerosis, scattered plasma cells, and a brisk lymphoeosinophilic infiltrate found dissecting between dense collagen bundles. This pattern of inflammation is an important clue that can guide the pathologist to look for focal herpetic viral changes in the epidermis, as patients with HIV possibly tend to amount a predominantly eosinophilic immune response in inflammatory skin conditions.

A pediatric case of unusual melanocytic proliferation of the nail.

Pigmentation of the nail plate, or melanonychia, is typically a benign condition caused by melanocyte activation. Although rare, melanonychia may be the initial presentation of melanoma, thus all cases require an in-depth examination. Evaluation in pediatric patients can prove especially difficult as benign cases have a higher prevalence of atypia compared to adults. Lack of specific treatment guidelines in the pediatric population can make diagnosis and treatment challenging. We report a pediatric patient with melanonychia with atypical features that required significant evaluations and collaboration to ultimately reach a treatment plan.

Generalized fixed drug eruption following Pfizer-BioNtech COVID-19 vaccination.

Fixed drug eruption is a cutaneous drug reaction which recurs at the same site when the individual is exposed to the causative drug, characterized by single or multiple round sharply demarcated erythematous-to-violaceous patches. Here, we report a patient with generalized non-bullous fixed drug eruption following mRNA-based Pfizer-BioNTech COVID-19 vaccine.

The pathology of malignant melanoma.

It is clear that much of what has been taught over the years concerning the pathology of melanoma may have little validity. Melanoma is viewed simply as a malignant neoplasm comprised initially of a proliferation of atypical melanocytes within the surface epithelium (epidermis). It has many features in common, regardless of anatomic site. It spreads within the epidermis first for months, possibly years or even for decades. At this stage (melanoma in situ) it is wholly curable if completely surgically excised. What determines how long a given melanoma remains in situ is not clear. It is probably a combination of factors, including host response to the neoplasm; physical barriers to growth and metastasis (perhaps solar damage); chemical or humoral growth factors or inhibitors (perhaps genetically determined); and other as yet undiscovered factors. Once a given neoplasm penetrates into the subjacent dermis, there are whole ranges of ill-defined events that act on its ability to continue to grow and develop the competence for metastasis (growth factors and inhibitors, neoangiogenesis factors and inhibitors, host immune responses, and so forth). Let us throw out all of our prejudices that may have developed or nurtured over the years. There is much to learn about the pathobiology of melanoma. Clinicians should keep their minds open to new concepts and try to separate what makes sense from that which does not.

Increased expression of enhancer of Zeste Homolog 2 (EZH2) differentiates squamous cell carcinoma from normal skin and actinic keratosis.

BACKGROUND: Enhancer of Zeste Homolog 2 (EZH2) is a polycomb group protein that has been shown to be involved in the progression of multiple human cancers including melanoma. The expression of EZH2 in normal skin and in pre-malignant and malignant cutaneous squamous cell carcinoma (SCC) has not been studied. OBJECTIVES: We examined the expression of EZH2 in normal skin, actinic keratosis (AK), SCC in situ, well-differentiated (SCC-WD), moderately-differentiated (SCC-MD) and poorly-differentiated SCC (SCC-PD) to ascertain whether EZH2 expression differentiates these conditions. MATERIALS AND METHODS: Immunohistochemical staining for EZH2 was performed on formalin-fixed paraffin-embedded biopsies and a tissue microarray containing normal skin, AK, SCC in situ, and SCC of different grades. RESULTS: In comparison to the normal skin, EZH2 expression in actinic keratosis was increased (p=0.03). Similarly, EZH2 expression in all of the neoplastic conditions studied (SCC in situ, SCC-WD, SCC-MD and SCC-PD) was greatly increased in comparison to both the normal skin and actinic keratosis (p≤0.001). CONCLUSION: EZH2 expression increases incrementally from normal skin to AK and further to SCC, suggesting a role for EZH2 in the progression and differentiation of SCC. EZH2 expression may be used as a diagnostic marker for differentiating SCC from AK or normal skin.

Dysplastic nevi.

Dysplastic nevi have been a subject of much debate since their original description in 1978. Although some question the biological potential of dysplastic nevi themselves, several studies have shown that their presence confers substantial risk for melanoma. In addition to predisposing patients to melanoma, dysplastic nevi have been shown to harbor genetic mutations, indicating their position on a continuum between banal nevi and melanomas. Dysplastic nevi are also clinically relevant as mimickers of melanoma, and can be challenging diagnostically. This article reviews the history, epidemiology, biology and genetics, clinical features, histopathologic features, and management guidelines for patients with these lesions.

The "dysplastic" nevus.

Dysplastic nevi have become an increasing focus clinically, with evidence that they are associated with a higher risk of developing melanoma. However, there still is contention regarding the significance of dysplastic nevi. This contribution provides an overview of the history, epidemiology, genetics, clinical and histologic features, and procedures for clinical management of dysplastic nevi. Since dysplastic nevi were described originally in 1978, a great deal of research has examined the epidemiology of these lesions and the genetic factors related to the development of dysplastic nevi. However, there is disagreement regarding the clinical management of dysplastic nevi and the histologic definition of dysplastic nevi. Current recommendations include preventative measures, such as sun protection and careful surveillance and biopsies of suspicious lesions as needed. The advent of new technologies, such as computer-vision systems, have the potential to significantly change treatment of dysplastic nevi in the future.

Granular parakeratosis: resolution with topical tretinoin.

Granular parakeratosis is an unusual acquired dermatosis characterized by intertriginous keratotic papules. Histologic examination shows parakeratosis with large numbers of basophilic keratohyaline granules within the stratum corneum. We report a case of a granular parakeratosis of the axilla that cleared rapidly with topical administration of tretinoin.

Neonatal pemphigus foliaceus.

The term "pemphigus" refers to a group of diseases that are characterized by the presence of cutaneous or mucosal blisters and erosions, and antiepidermal autoantibodies. There are several case reports of neonatal pemphigus vulgaris in the literature. Although pemphigus foliaceus antibodies have been shown to cross the placenta, to our knowledge, this is only the second reported case of neonatal pemphigus foliaceus. The proposed mechanism of disease transfer is the passive transfer of maternal IgG antibodies across the placenta.