Hematology/oncology Clinics of North America

Worldwide incidence rates of gestational trophoblastic disease (GTD) are difficult to estimate and compare due to large methodological differences within and between countries. Asia has generally reported higher incidence rates than Europe and North America, but modern reports have demonstrated a temporal decrease of GTD incidence rates in Asia and an increase in some European countries and North America. The main risk factors for hydatidiform mole are maternal age and previous molar events. Future studies on the epidemiology of GTD should include gestational trophoblastic neoplasia and international collaborative studies on this rare disease should be encouraged...

Complete and partial molar pregnancies arise from abnormal fertilization with marked proliferation of syncytiotrophoblasts. Earlier diagnosis has reduced the frequency of severe medical complications at presentation; however, the risk of progression to gestational trophoblastic neoplasia (GTN) has remained unchanged. Initial assessment should include serum hCG measurement after physical examination, laboratory testing for organ dysfunction, and Doppler ultrasound. Following uterine evacuation, pathologic assessment can distinguish complete from partial moles or non-molar gestations...

Majority of gestational trophoblastic neoplasia (GTN) follows molar pregnancies where diagnosis is mostly based on persistent or rising serum human chorionic gonadotrophin (hCG). Diagnosis of GTN could be based on clinical presentation, serum hCG measurement, imaging, histology, and genotyping. A high index of suspicion in women of reproductive age presenting with abnormal vaginal bleeding or unusual systematic presentation is important. An accurate staging and classification system for GTN is crucial to evaluate the risk and the prognosis of patients, and to optimize treatment...

Personalized neoantigen vaccines have achieved major advancements in recent years, with studies in melanoma leading progress in the field. Early clinical trials have demonstrated their feasibility, safety, immunogenicity, and potential efficacy. Advances in sequencing technologies and neoantigen prediction algorithms have substantively improved the identification and prioritization of neoantigens. Innovative delivery platforms now support the rapid and flexible production of vaccines. Several ongoing efforts in the field are aimed at improving the integration of large datasets, refining the training of prediction models, and ensuring the functional validation of vaccine immunogenicity...

Cutaneous imaging is a central tenant to the practice of dermatology. In this article, the authors explore various noninvasive and invasive skin imaging techniques, as well as the latest deployment of these technologies in conjunction with the use artificial intelligence and machine learning. The authors also provide insight into the benefits, limitations, and challenges around integrating these technologies into dermatologic practice.

Cutaneous T-cell lymphoma is a group of non-Hodgkin T-cell lymphomas that develop in and affect the skin but can potentially spread to other organs. There are many subtypes, the most common of which are mycosis fungoides, Sezary syndrome, lymphomatoid papulosis, and primary cutaneous anaplastic large cell lymphoma. Cutaneous lymphoma is a common cause of recalcitrant chronic skin rash and notoriously mimics other dermatologic and hematologic conditions, often resulting in diagnostic delays of months to years...

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that is highly radiosensitive and immunogenic. Immunotherapy is the primary treatment of advanced disease, and immune checkpoint inhibitors show promise as neoadjuvant or adjuvant therapy in patients with high-risk resectable MCC. Emerging biomarkers of tumor burden are becoming increasingly important in identifying high-risk patients and in post-treatment surveillance. Further research is needed to determine the optimal duration of anti-PD-(L)1 treatment and second-line options for patients with MCC refractory to immunotherapy...

Melanoma remains one of the most common cancers diagnosed in the United States, yet there have been substantial advancements in the treatment of resectable disease. Adjuvant therapy with immune checkpoint blockade (ICB) and targeted therapy with BRAF/MEK inhibitors (BRAF/MEKi) have now become standard of care for resectable stage IIIB-IV melanoma. In this article, the authors discuss recent scientific developments pertinent to the treatment of resectable melanoma including ICB, targeted therapy with BRAF/MEKi, oncolytic viruses, tumor-infiltrating lymphocyte therapy, and cancer vaccines...

Melanoma has seen the most remarkable therapeutic improvements among all cancers in the past decade, primarily due to the development of immune checkpoint inhibitors (ICI). Initially developed in the patients with advanced disease, ICI are now used in adjuvant and neoadjuvant settings. More recently, the development of LAG-3 blocking antibody and the combination of ICI with a personalized RNA-based vaccine have continued to lead the immunotherapeutic field. Despite these advances, primary and secondary resistances remain problematic and there is a high need for predictive biomarkers to optimize benefit/risk ratio of ICI use...

Primary cutaneous B-cell lymphomas represent a type of non-Hodgkin's lymphoma of the skin without evidence of extracutaneous involvement at the time of diagnosis. According to the 2018 World Health Organization-the European Organization for Research and Treatment of Cancer classification, primary cutaneous B-cell lymphomas include primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, intravascular large B-cell lymphoma, and Epstein-Barr virus+ mucocutaneous ulcer (provisional)...

Melanoma, a malignant tumor of melanocytes, poses a significant clinical challenge due to its aggressive nature and high potential for metastasis. The advent of targeted therapy has revolutionized the treatment landscape of melanoma, particularly for tumors harboring specific genetic alterations such as BRAF V600E mutations. Despite the initial success of targeted agents, resistance inevitably arises, underscoring the need for novel therapeutic strategies. This review explores the latest advances in targeted therapy for melanoma, focusing on new molecular targets, combination therapies, and strategies to overcome resistance...

Melanoma is the most commonly fatal type of skin cancer, and it is an important and growing public health problem in the United States and worldwide. Fortunately, incidence rates are decreasing in young people, stabilizing in middle-aged people, and increasing in older individuals. Herein, the authors further describe trends in melanoma incidence and mortality, review the literature on risk factors, and provide an up-to-date assessment of population-wide screening and new technology being utilized in melanoma screening...

The microbiome plays a substantial role in the efficacy of immune checkpoint blockade (ICB) in patients with metastatic melanoma. While the exact gut microbiome composition and the pathways involved in this interaction are not clearly delineated, novel studies and ongoing clinical trials are likely to reveal findings applicable to the clinical setting for the prediction and optimization of response to ICB. Nevertheless, lifestyle modifications, including high fiber diet, avoidance of unnecessary antibiotic prescriptions, and careful use of probiotics may be helpful to optimize the "health" of the gut microbiome and potentially enhance response to ICB in patients with melanoma...

Nonmelanoma skin cancers (NMSCs) are the most common cancers, with high-risk NMSCs sharing features such as poor histologic differentiation, invasion into deeper layers, and anatomic location. NMSC includes basal cell carcinoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma. Herein, the authors describe advances in understanding the genetic mechanisms of malignant transformation and the composition of tumor microenvironment for these cancers. They summarize recent therapeutic advances, including targeted therapy and immunotherapy for NMSCs...

Cutaneous melanoma is an aggressive form of skin cancer derived from skin melanocytes and is associated with significant morbidity and mortality. A significant fraction of melanomas are associated with precursor lesions, benign clonal proliferations of melanocytes called nevi. Nevi can be either congenital or acquired later in life. Identical oncogenic driver mutations are found in benign nevi and melanoma. While much progress has been made in our understanding of nevus formation and the molecular steps required for transformation of nevi into melanoma, the clinical diagnosis of benign versus malignant lesions remains challenging...

Pruritus, rash, and various other forms of dermatotoxicity are the most frequent adverse events among patients with cancer receiving targeted molecular therapy and immunotherapy. Immune checkpoint inhibitors, macrophage-targeting agents, and epidermal growth factor receptor/MEK inhibitors not only exert antitumor effects but also interfere with molecular pathways essential for skin immune homeostasis. Studying cancer therapy-induced dermatotoxicity helps us identify molecular mechanisms governing skin immunity and deepen our understanding of human biology...

In breast cancer (BC) pathogenesis models, normal cells acquire somatic mutations and there is a stepwise progression from high-risk lesions and ductal carcinoma in situ to invasive cancer. The precancer biology of mammary tissue warrants better characterization to understand how different BC subtypes emerge. Primary methods for BC prevention or risk reduction include lifestyle changes, surgery, and chemoprevention. Surgical intervention for BC prevention involves risk-reducing prophylactic mastectomy, typically performed either synchronously with the treatment of a primary tumor or as a bilateral procedure in high-risk women...

Precursor diseases of multiple myeloma (MM) are monoclonal gammopathy of uncertain significance and smoldering MM. While it is well known that a percentage of those affected by these conditions will progress to MM, it is difficult to predict who will progress and when, and guidelines for screening for these conditions are lacking. Moreover, there are various models for risk stratification, though there are ongoing efforts to improve these models in order to predict who may benefit from treatment. Finally, there are various clinical trials, both past and ongoing, expanding the scope of possible treatment options for precursor diseases...

Metastasis to the brain is a frequent complication of advanced melanoma. Historically, patients with melanoma brain metastasis (MBM) have had dismal outcomes, but outcomes have improved with the development of more effective treatments, including stereotactic radiosurgery and effective immune and targeted therapies. Despite these advances, MBM remains a leading cause of death from this disease, and many therapies show decreased efficacy against these tumors compared with extracranial metastases. This differential efficacy may be because of recently revealed unique molecular and immune features of MBMs-which may also provide rational new therapeutic strategies...

The skin consists of several cell populations, including epithelial, immune, and stromal cells. Recently, there has been a significant increase in single-cell RNA-sequencing studies, contributing to the development of a consensus Human Skin Cell Atlas. The aim is to understand skin biology better and identify potential therapeutic targets. The present review utilized previously published single-cell RNA-sequencing datasets to explore human skin's cellular and functional heterogeneity. Additionally, it summarizes the functional significance of newly identified cell subpopulations in processes such as wound healing and aging...