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Current Drug Safety Jun 2024Non-small Cell Lung Cancer (NSCLC) makes up about 85% of lung cancer cases, mainly adenocarcinoma and squamous cell carcinoma. Recently, PD-1 inhibitors have become...
BACKGROUND
Non-small Cell Lung Cancer (NSCLC) makes up about 85% of lung cancer cases, mainly adenocarcinoma and squamous cell carcinoma. Recently, PD-1 inhibitors have become crucial in NSCLC treatment, significantly enhancing survival for some. However, side effects, like skin reactions and hematotoxicity, limit their use, with drug-induced TEN and immunotherapy-induced agranulocytosis as severe adverse effects.
CASE PRESENTATION
Herein, we have reported the case of a 75-year-old male diagnosed with metastatic Lung Squamous cell Carcinoma (LUSC) in the left lung. He received first-line treatment with one cycle of tislelizumab in combination with nab-paclitaxel and carboplatin, after which he developed Toxic Epidermal Necrolysis (TEN) and granulocytopenia. To address these two serious immune-related Adverse Events (irAEs), the patient was administered methylprednisolone in combination with gamma globulin for TEN and dexamethasone in combination with G-CSF for agranulocytosis. Antibiotics were also administered according to the patient's medication regimen. After treatment, the patient recovered and was discharged from the hospital. It was also noted that the lung tumor condition improved.
CONCLUSION
Effective management of severe immune-related side effects from tislelizumab, including TEN and agranulocytosis, can be partly achieved through steroids, gamma globulin, GCSF, and antibiotics. This strategy not only alleviates these adverse effects, but also potentially improves tumor conditions, highlighting the crucial role of vigilant monitoring and management in immunotherapy.
PubMed: 38910480
DOI: 10.2174/0115748863297885240604111018 -
Hematology/oncology Clinics of North... Jun 2024Nonmelanoma skin cancers (NMSCs) are the most common cancers, with high-risk NMSCs sharing features such as poor histologic differentiation, invasion into deeper layers,... (Review)
Review
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. Effective skin protection against ultraviolet radiation-induced carcinogenesis remains an urgent unmet need for NMSC prevention. The authors highlight immune-based interventions as novel strategies to address this need.
PubMed: 38908957
DOI: 10.1016/j.hoc.2024.05.004 -
The Journal of Investigative Dermatology Jun 2024Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high mortality rate. MC polyomavirus (MCPyV) causes 80% of MCCs, encoding the viral oncogenes small T...
Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high mortality rate. MC polyomavirus (MCPyV) causes 80% of MCCs, encoding the viral oncogenes small T (sT) and truncated large T antigens (tLT). These proteins impair the Rb1-dependent G1/S checkpoint blockade and subvert the host cell epigenome to promote cancer. Whole proteome analysis and proximal interactomics identified a tLT-dependent deregulation of DNA damage response (DDR). Our investigation revealed a previously unreported interaction between tLT and the histone methyltransferase EHMT2, to our knowledge. T Antigens knockdown reduced DDR protein levels and increased levels of the DNA damage marker γH2Ax. EHMT2 normally promotes H3K9 methylation and DDR signaling. Given that inhibition of EHMT2 did not significantly change the MCC cells proteome, tLT-EHMT2 interaction could affect the DDR. With tLT, we report that EHMT2 gained DNA damage repair proximal interactors. EHMT2 inhibition rescued proliferation in MCC cells depleted for their T antigens, suggesting impaired DDR and/or lack of checkpoint efficiency. Combined tLT and EHMT2 inhibition led to altered DDR, evidenced by multiple signaling alterations. Here we show that tLT hijacks multiple components of the DNA damage machinery to enhance tolerance to DNA damage in MCC cells, which could explain the genetic stability of these cancers.
PubMed: 38908781
DOI: 10.1016/j.jid.2024.04.034 -
Archives of Dermatological Research Jun 2024Approximately 5-15% of all dermatologic malignancies manifest in the upper and lower eyelids. The primary types include basal cell carcinoma, squamous cell carcinoma,... (Review)
Review
Approximately 5-15% of all dermatologic malignancies manifest in the upper and lower eyelids. The primary types include basal cell carcinoma, squamous cell carcinoma, and sebaceous cell carcinoma, with Merkel cell carcinoma and melanoma following closely behind. Basal cell carcinoma predominantly affects the lower eyelid, yet various other carcinomas, melanomas, metastases, and neoplasms of diverse origins can arise on both upper and lower eyelids. Risk factors such as advanced age, smoking, and notably, exposure to UV light significantly contribute to the development of these eyelid lesions. Despite the increasing incidence, research on dermatologic eyelid malignancies remains limited. However, such study is imperative given that many systemic oncologic malignancies initially present as metastatic eyelid lesions. This paper provides an in-depth exploration of eyelid anatomy, clinical presentation, diagnosis, and treatment management.Key Points: Eyelid metastases represent less than one percent of all eyelid cancers, yet they often serve as the initial indication of an underlying systemic malignancy. Early detection and treatment is crucial in improving prognosis and quality of life for patients. Treatment options encompass a range of modalities, with Mohs surgery as the gold standard for the removal of ocular tumors. Additional treatment options include local excision as well as non-surgical interventions such as radiotherapy, cryotherapy, immunotherapy, and topical medications.
Topics: Humans; Eyelid Neoplasms; Eyelids; Mohs Surgery; Skin Neoplasms; Melanoma; Carcinoma, Merkel Cell; Risk Factors; Carcinoma, Basal Cell; Quality of Life; Carcinoma, Squamous Cell; Sebaceous Gland Neoplasms
PubMed: 38907769
DOI: 10.1007/s00403-024-03163-1 -
European Journal of Dermatology : EJD Apr 2024All tumour cells in a patient have shared and non-shared genetic alterations, and the diversity of mutations is described as intratumoural heterogeneity (ITH)....
All tumour cells in a patient have shared and non-shared genetic alterations, and the diversity of mutations is described as intratumoural heterogeneity (ITH). Multiregion sequencing is a genome sequencing analytical technique used for multiple, spatially-separated biopsy tissues that may further our understanding of ITH and tumour evolution. Although genetic mutations in extramammary Paget's disease (EMPD) have recently been detected by next-generation sequencing analysis, there have been no reports of ITH based on multiregion sequencing in EMPD. Thus, we clarified the landscape of ITH and tumour evolution in EMPD. We performed whole-exome sequencing on 35 tissues (30 tumour tissues and five normal skin samples as a paired control), collected from five patients with EMPD. The rate of private mutations was significantly higher than that of ubiquitous and shared mutations. Ubiquitous mutations were not present in driver genes, and most driver genes exhibited private and shared mutations. The most frequent base substitution was C>T in almost all lesions, and most mutational signatures corresponded to signature 1, 2, 3, and 8. The types of proposed aetiology in most lesions were based on age and AID/APOBEC family and BRCA1/BRCA2 mutations. Evolutionary trees were characterized by short trunks and long branches due to the extremely high ratio of private mutations. In contrast, pathogenic factors, such as base substitutions, mutational signatures, and proposed aetiology, were shared. Tumour evolution in EMPD appears to be characterized by a high level of genetic ITH with shared background factors.
Topics: Humans; Paget Disease, Extramammary; Skin Neoplasms; Clonal Evolution; Female; Aged; Mutation; Male; Genetic Heterogeneity; Exome Sequencing; Aged, 80 and over; Middle Aged
PubMed: 38907549
DOI: 10.1684/ejd.2024.4609 -
European Journal of Dermatology : EJD Apr 2024The clinical diagnosis of pigmented genital lesions is challenging. Reflectance confocal microscopy (RCM) is effective for diagnosis but is limited in its application... (Observational Study)
Observational Study Comparative Study
The clinical diagnosis of pigmented genital lesions is challenging. Reflectance confocal microscopy (RCM) is effective for diagnosis but is limited in its application due to elevated costs. A more affordable dermatoscope with a 400x magnification (D400) has recently been brought to market. The aim of our study was to compare these two imaging techniques for the analysis of pigmented genital tumours. An observational, prospective and mono-centric study was carried out from October 2017 to May 2019, in which clinical, dermatoscopic (20x and 400x) and RCM data from 207 pigmented genital lesions were collected. The images generated via D400 and RCM were analysed by three expert investigators. Similarities between the criteria observed using D400 and RCM were evaluated by each investigator. In total, 207 lesions were included: 183 melanosis, 19 nevi, one basal cell carcinoma (BCC), two condylomas and two melanomas in situ. Our series correlates well with data found in the literature especially for the distribution of different lesions, their topography, and their aspect using x20 dermatoscopy and RCM. Pattern and cell criteria defined using RCM largely paralleled those observed with D400 for all three investigators. Correlation between D400 and RCM was moderate to strong with regards to the identification of the ring pattern and clustered round cells, strong for dendritic and plump cells, and perfect for isolated round cells and spindle cells. D400 is an easy-to-use, cost-effective alternative for the analysis of pigmented genital lesions, particularly for melanosis.
Topics: Humans; Microscopy, Confocal; Dermoscopy; Melanosis; Prospective Studies; Skin Neoplasms; Female; Male; Melanoma; Carcinoma, Basal Cell; Middle Aged; Adult; Condylomata Acuminata; Nevus, Pigmented; Aged; Genital Diseases, Female; Nevus
PubMed: 38907542
DOI: 10.1684/ejd.2024.4663 -
Familial Cancer Jun 2024Fanconi anemia (FA) is an inherited bone marrow failure syndrome (IBMFS) characterized by pathogenic variants in the FA/BRCA DNA repair pathway genes. Individuals with...
Fanconi anemia (FA) is an inherited bone marrow failure syndrome (IBMFS) characterized by pathogenic variants in the FA/BRCA DNA repair pathway genes. Individuals with FA have an elevated risk of developing myelodysplastic syndrome, acute myeloid leukemia, and solid tumors. Hematopoietic cell transplantation (HCT) is the most effective treatment for FA related bone marrow failure but can increase the risk of cancer development. Information on benign tumors and NMSC is lacking in patients with FA. Our objective was to characterize patients with FA enrolled in the National Cancer Institute IBMFS Study who have experienced non-melanoma skin cancers (NMSC) and/or benign tumors (BT). A total of 200 patients diagnosed with FA were enrolled in the Institutional Review Board approved study "Etiologic Investigation of Cancer Susceptibility in IBMFS: A Natural History Study" (NCT00027274). Through medical records review, we identified 30 patients with at least one NMSC, either squamous or basal cell carcinoma, or benign tumor. The remaining 170 patients comprised the control group. Out of 200 patients, 12 had NMSC, 25 had benign tumors, with an age range of 11-64 and 0-56 years, respectively. The median age at HCT was 30.5 years for NMSC patients, 9 years for benign tumor patients, and 9.1 years for controls. The most common genotype observed was FANCA, followed by FANCC and FANCI. Benign tumors spanned diverse anatomical locations. Early onset NMSC in patients with FA compared to the general population emphasizes the need for consistent monitoring in patients with FA, while the diverse anatomical locations of benign tumors underscore the importance of comprehensive surveillance for timely interventions in managing symptomatology and heightened cancer risk.
PubMed: 38907138
DOI: 10.1007/s10689-024-00410-2 -
Critical Reviews in Oncology/hematology Jun 2024Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and... (Review)
Review
CONTEXT
Genitourinary cancers (GUCs) encompass malignancies affecting the urinary and reproductive systems, including renal cell carcinoma (RCC), urothelial carcinoma (UC), and prostate cancer (PC). With the rapidly evolving therapeutic domain of these cancers, cutaneous adverse events (AEs) remain among the most observed toxicities.
OBJECTIVE
To explore the dermatologic AEs linked to novel GUC treatments, their underlying pathophysiology, clinical presentations, and risk factors.
EVIDENCE ACQUISITION
A narrative review of the literature from PubMed and Embase databases was conducted. The search strategy included dermatologic/cutaneous adverse events, risk factors, and pathophysiology in conjunction with the following classes of therapies; immune checkpoint inhibitors (ICIs), antiangiogenic therapies, enfortumab vedotin (EV), erdafitinib, and androgen receptor antagonists (ARAs).
EVIDENCE SYNTHESIS
Maculopapular rash, pruritus, and alopecia are present among the five classes of therapies. ICIs demonstrate the highest incidence of severe drug AEs including Steven Johnson syndrome/toxic epidermal necrolysis. Unique cutaneous AEs present with specific therapies including hand-foot skin reaction and subungual splinter hemorrhage with antiangiogenic drugs, stomatitis/mucositis and onycholysis with erdafitinib. Incidence and type of cutaneous AE also differed within therapies in the same class as seen with apalutamide displaying the highest risk of cutaneous AEs within ARAs. Risk factors for development of cutaneous AEs can be general to therapies, or specific, and include age, immune status, BMI, and gender.
CONCLUSIONS
Dermatologic AEs may impact patients' quality of life and increase the tendency to dose reduce, hold or discontinue life-saving therapies, underscoring the need for vigilant monitoring, early recognition, and collaborative management between medical oncologists, pharmacists, dermatologists and other specialists.
PubMed: 38906514
DOI: 10.1016/j.critrevonc.2024.104420 -
Journal of the American Academy of... Jun 2024
PubMed: 38906257
DOI: 10.1016/j.jaad.2024.05.089