Cutaneous Melanocytic Tumor with CRTC1::TRIM11 Fusion: Review of the Literature of a Potentially Novel Entity

“Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion” (CMTCT) is a recently described entity belonging to the family of superficial tumors displaying melanocytic differentiation. Thirteen cases have been reported so far, on the head and neck, extremities, and trunk of adults of all ages (12 cases) and one in an 11-year-old child. Histopathologically, it is a nodular or multilobulated tumor composed of spindle and epithelioid cells arranged in nests, fascicles, or bundles that are surrounded by thin collagenous septa. By immunohistochemistry, the tumor shows variable immunoreactivity for S100-protein, SOX10, and MITF, as well as specific melanocytic markers such as MelanA and HMB-45. The neoplasm’s biologic behavior remains uncertain since the reported cases are limited and the follow-up is short (median 12 months). However, local recurrence and synchronous distant metastasis after 13 years of initial resection has been described in one case. Herein, we present a comprehensive literature review of CMTCT hoping to raise awareness among the dermatopathologists of this potentially novel entity.

Melan-A Expression in Poorly Differentiated Carcinoma of Lung: A Potential Diagnostic Pitfall

BackgroundMelan-A/MART-1 is a melanocytic differentiation marker, which is recognized as an antigen on melanoma cells. It is relevant for pathologists as a useful diagnostic marker in the diagnosis of melanocytic tumors. However, the expressional pattern of Melan-A in poorly differentiated carcinoma of lung has never been reported so far.Case presentationHere, we report a 77-year-old female patient who presented with a large mass in the right lung and was subsequently diagnosed with a poorly differentiated carcinoma of lung. We unexpectedly found that the carcinoma in this patient exhibited diffuse Melan-A expression. ConclusionThis is the first case reported of a poorly differentiated carcinoma of lung with Melan-A expression. This report shows that Melan-A can express in poorly differentiated carcinoma, and highlights a potential diagnostic pitfall in the diagnosis of carcinoma, which urges pathologists to exercise caution in cases where Melan-A positivity and illustrates the need for further immunohistochemical or molecular examination to avoid misdiagnosis.

Microphthalmia-Associated Transcription Factor in Senescence and Age-Related Diseases

Although microphthalmia-associated transcription factor (MITF) has been known for decades as a key regulator for melanocytic differentiation, recent studies expanded its other roles in multiple biological processes. Among these newfound roles, the relationship between MITF and aging is attractive; however, the underlying mechanism remains elusive. Here, we review the documented cues that highlight the implication of MITF in the aging process and particularly discuss the possible mechanisms underlying the participation of MITF in cellular senescence. First, it summarizes the association of MITF with melanocytic senescence, including the roles of MITF in cell cycle regulation, DNA damage repair, oxidative stress response, and the generation of senescence-associated secretory phenotype. Then, it collects the information involving MITF-related senescent changes in nonmelanocytes, such as retinal pigment epithelium cells, osteoclasts, and cardiomyocytes. This review may deepen the understanding of MITF function and be helpful to develop new strategies for improving geriatric health.

High-grade Urothelial Carcinoma with Malignant Melanocytic Differentiation

Urothelial carcinoma usually shows divergent differentiation and variant histology with squamous and glandular morphology being most common. In this report, we present a case of divergent malignant melanocytic differentiation in a high-grade urothelial carcinoma. A 98-year-old East Asian woman with an anterior bladder wall mass underwent resection, which revealed a high-grade poorly differentiated tumor. A minor component of high-grade papillary urothelial carcinoma and carcinoma in situ is also present. The majority of the tumor cells are morphologically and immunohistochemically consistent with melanoma, a minority of cells are positive for urothelial markers, and rare cells coexpress both melanocytic and urothelial markers. Cells that express melanocytic markers or urothelial markers are intimately admixed together. Taken together, a diagnosis of high-grade urothelial carcinoma with malignant melanocytic differentiation was rendered. This is the first report in the literature of malignant melanocytic differentiation in a high-grade urothelial carcinoma, a finding that may have important diagnostic and therapeutic implications.

Insights into Differentiation of Melanocytes from Human Stem Cells and Their Relevance for Melanoma Treatment

Malignant melanoma represents a highly aggressive form of skin cancer. The metastatic process itself is mostly governed by the so-called epithelial mesenchymal transition (EMT), which confers cancer cells migrative, invasive and resistance abilities. Since EMT represents a conserved developmental process, it is worthwhile further examining the nature of early developmental steps fundamental for melanocyte differentiation. This can be done either in vivo by analyzing the physiologic embryo development in different species or by in vitro studies of melanocytic differentiation originating from embryonic human stem cells. Most importantly, external cues drive progenitor cell differentiation, which can be divided in stages favoring neural crest specification or melanocytic differentiation and proliferation. In this review, we describe ectopic factors which drive human pluripotent stem cell differentiation to melanocytes in 2D, as well as in organoid models. Furthermore, we compare developmental mechanisms with processes described to occur during melanoma development. Finally, we suggest differentiation factors as potential co-treatment options for metastatic melanoma patients.