Removal of Incidental Skin Cancer During Mohs Micrographic Surgery Indicated for a Different Primary Tumor.

BACKGROUND: Mohs surgery is a tissue-sparing, microscopically controlled procedure used to treat biopsy-proven skin cancers. Because Mohs surgery allows for examination of the complete margin of each tissue layer removed, separate cancers can be treated concomitantly when identified. As early detection of skin cancer is beneficial for reducing morbidity, incidental tumors discovered during Mohs surgery are of significant interest. OBJECTIVE: Our objective was to determine the prevalence and characteristics of incidental skin cancers found during Mohs surgery. METHODS: A retrospective chart review of cases seen at University of California, San Diego, from 2014 to 2021 was performed. RESULTS: Of 13,464 Mohs surgery cases, 4.53% ( n = 610) had incidental skin cancers found during removal of the initially identified tumor. Of the 610 cases, 88.4% ( n = 539) had basal cell carcinoma as the primary tumor and either squamous cell carcinoma (SCC) or SCC in situ as the incidental tumor. About 7.87% ( n = 48) had SCC as the primary tumor and basal cell carcinoma as the incidental tumor. All tumors were removed with clear margins and without significant complications. CONCLUSION: Diagnosis of incidental tumors during Mohs surgery enables early detection of skin cancer and circumvents the need for additional surgery, likely resulting in decreased morbidity and improved cost-effectiveness.

Combined lineage tracing and scRNA-seq reveals unexpected first heart field predominance of human iPSC differentiation.

During mammalian development, the left and right ventricles arise from early populations of cardiac progenitors known as the first and second heart fields, respectively. While these populations have been extensively studied in non-human model systems, their identification and study in vivo human tissues have been limited due to the ethical and technical limitations of accessing gastrulation-stage human embryos. Human-induced pluripotent stem cells (hiPSCs) present an exciting alternative for modeling early human embryogenesis due to their well-established ability to differentiate into all embryonic germ layers. Here, we describe the development of a TBX5/MYL2 lineage tracing reporter system that allows for the identification of FHF- progenitors and their descendants including left ventricular cardiomyocytes. Furthermore, using single-cell RNA sequencing (scRNA-seq) with oligonucleotide-based sample multiplexing, we extensively profiled differentiating hiPSCs across 12 timepoints in two independent iPSC lines. Surprisingly, our reporter system and scRNA-seq analysis revealed a predominance of FHF differentiation using the small molecule Wnt-based 2D differentiation protocol. We compared this data with existing murine and 3D cardiac organoid scRNA-seq data and confirmed the dominance of left ventricular cardiomyocytes (>90%) in our hiPSC-derived progeny. Together, our work provides the scientific community with a powerful new genetic lineage tracing approach as well as a single-cell transcriptomic atlas of hiPSCs undergoing cardiac differentiation.

A crack in the armor: Wolf isotopic response manifesting as cutaneous lupus.

Wolf isotopic response represents the development of skin lesions of one particular morphology occurring at the same site as another morphologically distinct and unrelated skin lesion. Cutaneous lupus erythematosus (CLE) is an autoimmune connective tissue disorder encompassing a wide range of phenotypes that may be associated with systemic involvement. Although CLE is a well-described entity with a broad spectrum, the occurrence of lesions manifesting as an isotopic response is rare. We present a patient with systemic lupus erythematosus who developed CLE in a dermatomal distribution following herpes zoster. When CLE lesions present in a dermatomal distribution, these cases may be difficult to distinguish from recurrent herpes zoster infection in an immunosuppressed patient. Therefore, they pose a diagnostic challenge and require balancing antiviral therapy with immunosuppression to sufficiently maintain adequate control of the autoimmune disease while addressing possible infections. To avoid treatment delay, clinicians should have elevated suspicion for an isotopic response when disparate lesions erupt in areas previously affected by herpes zoster or in cases of persistent eruptions at sites of prior herpes zoster. We discuss this case within the context of Wolf isotopic response and review the literature for similar cases.

Non-medication Acquired Sticky Skin: Case Report of Idiopathic Acquired Cutaneous Adherence and Review of Medication-Induced Sticky Skin.

Sticky skin is a dermatologic phenomenon in which the skin may cause objects to adhere to it on contact or adhere to itself or both. The entire skin can be affected in patients with sticky skin. Alternatively, just acral sites, such as the hand, can be involved. The acquisition of sticky skin has been described in patients treated with certain medications. These drugs include retinoids, proton pump inhibitors, and antifungals; they also include combination therapy utilizing an antineoplastic agent and an antifungal drug in patients with hormone-resistant prostate cancer. The pathogenesis of acquired cutaneous adherence in patients with androgen-independent prostate cancer was postulated to be the result of therapy-induced elevation of endogenous retinoids. Retinoids have multiple biological effects on epidermal differentiation that may contribute to the pathogenesis of acquired cutaneous adherence. These include the induction of fine, granular, mucus-like deposits within and between the keratinocytes in the upper stratum spinosum and stratum corneum, modulation of lipid composition in keratinocytes, prevention of cross-linked, cornified envelope formation in keratinocytes by the inhibition of epidermal transglutaminase, and altered and decreased content of keratin within the epidermis. We describe an older man who developed non-medication acquired sticky skin (NoMasts). His acquired cutaneous adherence was considered to be idiopathic. We postulate that aging may be associated with elevated endogenous retinoid levels in older individuals and may have resulted in his sticky skin. Further investigation into these retinoid-induced effects and to what extent they promote acquired cutaneous adherence is still needed.

Purification of Pluripotent Stem Cell-Derived Cardiomyocytes Using CRISPR/Cas9-Mediated Integration of Fluorescent Reporters.

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes have become critically important for the detailed study of cardiac development, disease modeling, and drug screening. However, directed differentiation of hiPSCs into cardiomyocytes often results in mixed populations of cardiomyocytes and other cell types, which may confound experiments that require pure populations of cardiomyocytes. Here, we detail the use of a CRISPR/Cas9 genome editing strategy to develop cardiomyocyte-specific reporters that allow for the isolation of hiPSC-derived cardiomyocytes and chamber-specific myocytes. Moreover, we describe a cardiac differentiation protocol to derive cardiomyocytes from hiPSCs, as well as a strategy to use fluorescence-activated cell sorting to isolate pure populations of fluorescently labeled cardiomyocytes for downstream applications.

Blaschkolinear Acquired Inflammatory Skin Eruption (BLAISE): Case Report of a Young Man Whose Dermatosis had Features of Lichen Striatus and Blaschkitis.

Cutaneous conditions can follow Blaschko's lines on the skin, which are thought to reflect patterns of cell migration and clonal expansion during embryonic development of the epidermis. These diseases are hypothesized to be caused by genetic mosaicism resulting from processes such as lyonization or somatic postzygotic mutation. Lichen striatus and blaschkitis are two such acquired inflammatory skin disorders that are distinguished in the literature by age of onset, location, and histopathological features. Lichen striatus is typically observed on the extremities of children and is characterized by lichenoid papules that appear in a linear distribution along Blaschko's lines. Microscopic examination typically shows spongiosis, as well as lichenoid and periadnexal inflammation. Blaschkitis more commonly occurs in adults and frequently involves the truncal areas, including the chest and abdomen. Microscopic examination typically shows spongiotic dermatitis. We describe a young man with a linear eruption extending from the flexor aspect of his right wrist to his central chest, which has features of both lichen striatus and blaschkitis. Both lichen striatus and blaschkitis are self-limited diseases that may resolve within months. It has been suggested that lichen striatus and blaschkitis are not separate entities, but rather the two endpoints within the spectrum of blaschkolinear acquired inflammatory skin eruption (BLAISE). The overlapping features of lichen striatus and blaschkitis in our patient demonstrate the spectrum of clinical and pathologic features in patients with BLAISE.

New Onset of Linear Purpura on the Back: Coining Therapy-Associated Ecchymoses.

Coining therapy is a treatment commonly used in complementary and alternative medicine. The practice has its origins in several different Asian countries. It is used to treat numerous conditions, such as chronic pain, fever, flu, headaches, heatstroke, and upper respiratory infections. Coining is performed by vigorously rubbing a rounded instrument following the application of lubricant to the affected area. Hence, patients who have undergone coining therapy frequently present with macular erythema, petechiae, and/or raised ecchymoses at the sites of treatment. The cutaneous sequelae following treatment with coining on a Vietnamese man are described. Ecchymoses caused by coining usually resolve spontaneously within one to two weeks. While coining is generally regarded as a safe practice, mild or - albeit rarely - more severe complications may occur. Therefore, this procedure is contraindicated in certain patients including those with bleeding disorders, Von Willebrand disease, or those taking antiplatelet or anticoagulant medications. Several randomized-control studies suggest coining to be an effective treatment for chronic neck and lower back pain. Immediate pain relief at the treated site may result from increased circulation; thus, the venting of heat may mitigate the effects of the inflammation and pain. However, much remains to be learned about the mechanisms of longer-term pain relief in coining therapy. The use of complementary and alternative medicine techniques such as coining has increased in the United States; therefore, clinicians' evaluation and management of their patients would benefit from an understanding of the individual's sociocultural practices and health beliefs.

Simple Lithography-Free Single Cell Micropatterning using Laser-Cut Stencils.

Micropatterning techniques have been widely used in cell biology to study effects of controlling cell shape and size on cell fate determination at single cell resolution. Current state-of-the-art single cell micropatterning techniques involve soft lithography and micro-contact printing, which is a powerful technology, but requires trained engineering skills and certain facility support in microfabrication. These limitations require a more accessible technique. Here, we describe a simple alternative lithography-free method: stencil-based single cell patterning. We provide step-by-step procedures including stencil design, polyacrylamide hydrogel fabrication, stencil-based protein incorporation, and cell plating and culture. This simple method can be used to pattern an array of as many as 2,000 cells. We demonstrate the patterning of cardiomyocytes derived from single human induced pluripotent stem cells (hiPSC) with distinct cell shapes, from a 1:1 square to a 7:1 adult cardiomyocyte-like rectangle. This stencil-based single cell patterning is lithography-free, technically robust, convenient, inexpensive, and most importantly accessible to those with a limited bioengineering background.