MLL4 is a critical mediator of differentiation and ferroptosis in the epidermis

The epigenetic regulator, MLL4 (KMT2D), has been described as an essential gene in both humans and mice. In addition, it is one of the most commonly mutated genes in all of cancer biology. Here, we identify a critical role for Mll4 in the promotion of epidermal differentiation and ferroptosis, a key mechanism of tumor suppression. Mice lacking epidermal Mll4, but not the related enzyme Mll3 (Kmt2c), display features of impaired differentiation and human pre-cancerous neoplasms, including epidermal hyperplasia, atypical keratinocytes, and a loss of polarization, all of which progress with age. Mll4 deficiency profoundly alters epidermal gene expression, and uniquely rewires the expression of key genes and markers of ferroptosis (Alox12, Alox12b, Aloxe3). Beyond identifying a novel role for Mll4-mediated tumor suppression in the skin, our data reveal a potentially much more broad and general role for ferroptosis in the process of epidermal differentiation and skin homeostasis.

Pseudoangiosarcomatous squamous cell carcinoma: first case report on penis.

Background: Pseudoangiosarcomatous squamous cell carcinoma, also called pseudovascular, pseudoangiomatoid or adenoid pseudovascular carcinoma, is an uncommon and highly aggressive variant of squamous cell carcinoma. Histologically, it is characterized by proliferation of atypical keratinocytes with acantholysis and formation of pseudovascular spaces, forming anastomosed channels lined with neoplastic cells that invade the dermis. These cells are positive for cytokeratin and vimentin and negative for vascular markers such as CD31 and CD34. There are few reports of this tumor variant in the literature. Skin, breast, lung and vulva involvement have been described. But to the best of our knowledge, no cases involving the penis have been described. This article aims to describe the first case of angiosarcomatous squamous cell carcinoma of the penis. Case Report: The patient presented with a painful lesion in the penis associated with urinary retention. Macroscopic findings exhibited an ulcerative vegetating lesion that involving the entire glans and part of the penile body, as well as infiltration of penile structures and scrotal skin. Microscopy shows atypical proliferation of sarcomatous keratinocyte pattern mimicking vascular spaces. These neoplastic squamous cells were positive for the cytokeratin marker and were negative for the CD31 and CD34 markers. Human papilloma virus biomarkers, p16, E6 protein and PCR, were all negative. Conclusion: This report presents the first reported case of penile pseudoangiosarcomatous squamous cell carcinoma, as an important differential diagnosis.

Recurrent Multiple Squamous Cell Carcinomas on the Scalp in a Patient with Juvenile Dermatomyositis

Both long-term administration of immunosuppressive agents and chronic inflammatory conditions, such as autoimmune disease, could be risk factors for the development of cutaneous squamous cell carcinoma (cSCC). In this report, we present a case of recurrent multiple cSCC on the scalp in a patient with juvenile dermatomyositis who had been administered cyclosporine and Predonine since she was a 1-year-old infant. Interestingly, immunohistochemical staining revealed IL-17-producing cells adjacent to IL-17R-expressing atypical keratinocytes. Our present case suggested that IL-17/IL-17R signaling might contribute to the carcinogenesis of cSCC.

Actinic Keratosis: A New Approach to the Treatment / Aktinična Keratoza: Novi Pristup Lečenju

Actinic keratosis is an intraepidermal proliferation of transformed, atypical keratinocytes, induced by exposure to solar ultraviolet radiation. Many authors believe that it is the earliest form of squamous cell carcinoma. More than 40% of all metastatic squamous cell carcinomas develop from actinic keratosis. The clinical, histological and molecular characteristics of actinic keratosis are those of squamous cell carcinomas. Since it can be extremely hard to distinguish actinic keratosis from some squamous cell carcinomas, treatment can be rather difficult. The best treatment of actinic keratosis is its prevention. The main reason for therapy which is universally accepted, is prevention of squamous cell carcinoma. A number of options are available, but when considering the efficacy, invasive procedures remain the standard treatment. Treatment of individual lesions may prevent further progression of actinic damage present in the surrounding skin