Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma.

Macrophage Migration Inhibitory Factor (MIF) and its homolog D-dopachrome Tautomerase (DDT) have been implicated as drivers of tumor progression across a variety of cancers. Recent evidence suggests MIF as a therapeutic target in immune checkpoint inhibition (ICI) resistant melanomas, however clinical evidence of MIF and particularly of DDT remain limited. This retrospective study analyzed 97 patients treated at Yale for melanoma between 2002-2020.

NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2024.

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.

Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma.

Background: Desmoplastic melanoma (DM) is a rare melanoma subtype characterized by dense fibrous stroma, a propensity for local recurrence, and a high response rate to programmed cell death protein 1 (PD-1) blockade. Occult sentinel lymph node positivity is significantly lower in both pure and mixed DM than in conventional melanoma, underscoring the need for better prognostic biomarkers to inform therapeutic strategies.

Methods: We assembled a tissue microarray comprising various cores of tumor, stroma, and lymphoid aggregates from 45 patients with histologically confirmed DM diagnosed between 1989 and 2018.

Predictive accuracy of elevated mitotic rate on lymph node positivity and recurrence in thin melanomas.

Background: Mitotic rate (MR) is considered an important prognostic factor for melanoma but is not currently used for staging because its nuanced effect is not yet well-delineated. We sought to determine if T category-specific MR is predictive of sentinel lymph node (SLN) positivity, recurrence, and melanoma-specific mortality (MSM).

Methods: A retrospective review of patients with primary cutaneous melanoma from 1994 to 2020 at a single academic center was performed.

Chronic UV radiation-induced RORγt+ IL-22-producing lymphoid cells are associated with mutant KC clonal expansion.

Chronic ultraviolet (UV) radiation exposure is the greatest risk factor for cutaneous squamous cell carcinoma (cSCC) development, and compromised immunity accelerates this risk. Having previously identified that epidermal Langerhans cells (LC) facilitate the expansion of UV-induced mutant keratinocytes (KC), we sought to more fully elucidate the immune pathways critical to cutaneous carcinogenesis and to identify potential targets of intervention. Herein, we reveal that chronic UV induces and LC enhance a local immune shift toward RORγt+ interleukin (IL)-22/IL-17A-producing cells that occurs in the presence or absence of T cells while identifying a distinct RORγt+ Sca-1+ CD103+ ICOS+ CD2 CCR6+ intracellular CD3+ cutaneous innate lymphoid cell type-3 (ILC3) population (uvILC3) that is associated with UV-induced mutant KC growth.

Merkel Cell Carcinoma: Changing Practice Patterns and Impact on Recurrence-Free and Overall Survival at a Single Institution and Nationally.

Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. Our report describes the evolution of management and characteristics associated with recurrence, disease-specific survival (DSS) and overall survival (OS) in the treatment of MCC.

Methods: A single institution retrospective review of MCC and SEER data to determine factors associated with RFS, DSS, and OS using a multivariable Cox regression on inverse-probability weighted cohorts.

A melanoma patient with macrophage-cancer cell hybrids in the primary tumor, a lymph node metastasis and a brain metastasis.

In 1911 it was proposed that cancer might result from fusion and hybridization between macrophages and cancer cells. Using immunohistochemistry it was determined that essentially all solid tumors expressed macrophage-like molecules on their cell surface. More recently we have used forensic (STR) genetics that allows one to detect DNA from more than one individual in the same sample.

Delayed Localized Hypersensitivity Reactions to the Moderna COVID-19 Vaccine: A Case Series.

Importance: In response to the coronavirus disease 2019 (COVID-19) pandemic, 2 mRNA vaccines (Pfizer-BioNTech and Moderna) received emergency use authorization from the US Food and Drug Administration in December 2020. Some patients in the US have developed delayed localized cutaneous vaccine reactions that have been dubbed "COVID arm."

Objective: To describe the course of localized cutaneous injection-site reactions to the Moderna COVID-19 vaccine, subsequent reactions to the second vaccine dose, and to characterize the findings of histopathologic examination of the reaction.

NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2021.

Over the past few years, the NCCN Guidelines for Melanoma: Cutaneous have been expanded to include pathways for treatment of microscopic satellitosis (added in v2.2020), and the following Principles sections: Molecular Testing (added in v2.2019), Systemic Therapy Considerations (added in v2.

Dermatofibrosarcoma protuberans in pregnancy: a case series and review of the literature.

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma, which has been reported in pregnancy. This case series reports the clinical and histopathological findings of DFSP in pregnancy.

Methods: Eighteen cases of DFSP, including six unreported cases and 12 cases from the literature, were identified.

Cutaneous Involvement in Plasma Cell Myeloma.

Objectives: Plasma cell myeloma (PCM) involving skin is rare and occurs in 1% to 4% of patients with PCM. We evaluated the clinicopathologic features, cytogenetic findings and clinical follow-up in a series of PCM cases with cutaneous involvement.

Methods: Cases of PCM with cutaneous involvement were retrospectively reviewed with clinical data.

Acral Lentiginous Melanoma: Do Surgical Approach and Sentinel Lymph Node Biopsy Matter?

Unlabelled: Management of acral lentiginous melanoma (ALM) remains controversial. Traditionally, ALM was managed with digit amputation (DA), resulting in significant morbidity, but recent evidence has advocated for digit sparing management. Furthermore, the significance of nodal metastasis for ALM is not well reported.

Recent Advances in Studies of Skin Color and Skin Cancer.

The relationship between skin color and skin cancer is well established: the less melanin in one's skin the greater the risk for developing skin cancer. This review is in two parts. First, we summarize the current understanding of the cutaneous pigmentary system and trace melanin from its synthesis in the pigment cell melanosomes through its transfer to keratinocytes.

NCCN Guidelines Insights: Uveal Melanoma, Version 1.2019.

The NCCN Guidelines for Uveal Melanoma include recommendations for staging, treatment, and follow-up of patients diagnosed with uveal melanoma of the choroid or ciliary body. In addition, because distinguishing between uveal melanoma and benign uveal nevi is in some cases difficult, these guidelines also contain recommendations for workup of patients with suspicious pigmented uveal lesions, to clarify the tests needed to distinguish between those who should have further workup and treatment for uveal melanoma versus those with uncertain diagnosis and low risk who should to be followed and later reevaluated. These NCCN Guidelines Insights describe recommendations for treatment of newly diagnosed nonmetastatic uveal melanoma in patients who have already undergone a complete workup.

Human keratinocyte carcinomas have distinct differences in their tumor-associated macrophages.

Unlabelled: Cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) have different clinical behaviors, despite both being keratinocyte carcinomas mainly caused by ultraviolet radiation. Whether these distinct features are associated with tumor-associated macrophages (TAMs) is largely unknown. The main goal of this study was to conduct a comprehensive analysis of density and polarization states of TAMs in SCCs BCCs.

Janus kinase inhibition induces disease remission in cutaneous sarcoidosis and granuloma annulare.

Background: Sarcoidosis and granuloma annulare (GA) are cutaneous granulomatous disorders that can be difficult to treat. There is evidence of underlying Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway activation in sarcoidosis, suggesting that JAK inhibition might be effective.

Objective: To evaluate treatment with tofacitinib, a JAK inhibitor, in patients with recalcitrant sarcoidosis and GA.

Cutaneous Melanoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.

Tofacitinib Treatment and Molecular Analysis of Cutaneous Sarcoidosis.

There is evidence that Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling plays a role in the pathogenesis of sarcoidosis. We treated a patient with cutaneous sarcoidosis with the JAK inhibitor tofacitinib; the patient had not previously had a response to medications and had not received systemic glucocorticoids. This treatment resulted in clinical and histologic remission of her skin disease.