A rare case of leptomeningeal carcinomatosis in a patient with uveal melanoma: case report and review of literature

Fedorenko, Inna V.; Evernden, Brittany; Kenchappa, Rajappa S.; Sahebjam, Solmaz; Ryzhova, Elena; Puskas, John; Mcintosh, L. G.; Cáceres, Gisela; Magliocco, Anthony M.; Etame, Arnold B.; Harbour, J. William; Smalley, Keiran S.M.

doi:10.1097/cmr.0000000000000274

Cited by 10 publications

(7 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, CSF circulating tumor DNA (ctDNA) has been identified in the CSF of LMM patients and could be utilized diagnostically or prognostically [ 86 , 87 ]. ctDNA detection in the CSF of LMD is useful as a diagnostic, prognostic biomarker and can be relevant to identify the tumor-bearing mutations at different tumor stages.…”

Section: Lmd Diagnosismentioning

confidence: 99%

Leptomeningeal Disease (LMD) in Patients with Melanoma Metastases

Khaled

Tarhini

Smalley

et al. 2023

Cancers

Self Cite

View full text Add to dashboard Cite

Leptomeningeal disease (LMD) is a devastating complication caused by seeding malignant cells to the cerebrospinal fluid (CSF) and the leptomeningeal membrane. LMD is diagnosed in 5–15% of patients with systemic malignancy. Management of LMD is challenging due to the biological and metabolic tumor microenvironment of LMD being largely unknown. Patients with LMD can present with a wide variety of signs and/or symptoms that could be multifocal and include headache, nausea, vomiting, diplopia, and weakness, among others. The median survival time for patients with LMD is measured in weeks and up to 3–6 months with aggressive management, and death usually occurs due to progressive neurologic dysfunction. In melanoma, LMD is associated with a suppressive immune microenvironment characterized by a high number of apoptotic and exhausted CD4+ T-cells, myeloid-derived suppressor cells, and a low number of CD8+ T-cells. Proteomics analysis revealed enrichment of complement cascade, which may disrupt the blood–CSF barrier. Clinical management of melanoma LMD consists primarily of radiation therapy, BRAF/MEK inhibitors as targeted therapy, and immunotherapy with anti-PD-1, anti-CTLA-4, and anti-LAG-3 immune checkpoint inhibitors. This review summarizes the biology and anatomic features of melanoma LMD, as well as the current therapeutic approaches.

show abstract

Section: Lmd Diagnosismentioning

confidence: 99%

Leptomeningeal Disease (LMD) in Patients with Melanoma Metastases

Khaled

Tarhini

Smalley

et al. 2023

Cancers

Self Cite

View full text Add to dashboard Cite

show abstract

“…In brief, CTCs in CSF from patients with LMD were detected by adapting the CellSearch system (Janssen Diagnostics, Raitan, NJ, USA) using the CELLTRACKS Circulating Melanoma Cell Kit as previously described. 11 …”

Section: Methodsmentioning

confidence: 99%

A preclinical model of patient-derived cerebrospinal fluid circulating tumor cells for experimental therapeutics in leptomeningeal disease from melanoma

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background Leptomeningeal disease (LMD) occurs as a late complication of several human cancers and has no rationally designed treatment options. A major barrier to developing effective therapies for LMD is the lack of cell-based or preclinical models that recapitulate human disease. Here, we describe the development of in vitro and in vivo cultures of patient-derived cerebrospinal fluid circulating tumor cells (PD-CSF-CTCs) from patients with melanoma as a preclinical model to identify exploitable vulnerabilities in melanoma LMD. Methods CSF-CTCs were collected from melanoma patients with melanoma-derived LMD and cultured ex vivo using human meningeal cell–conditioned media. Using immunoassays and RNA-sequencing analyses of PD-CSF-CTCs, molecular signaling pathways were examined and new therapeutic targets were tested for efficacy in PD-CSF-CTCs preclinical models. Results PD-CSF-CTCs were successfully established both in vitro and in vivo. Global RNA analyses of PD-CSF-CTCs revealed several therapeutically tractable targets. These studies complimented our prior proteomic studies highlighting IGF1 signaling as a potential target in LMD. As a proof of concept, combining treatment of ceritinib and trametinib in vitro and in vivo demonstrated synergistic antitumor activity in PD-CSF-CTCs and BRAF inhibitor-resistant melanoma cells. Conclusions This study demonstrates that CSF-CTCs can be grown in vitro and in vivo from some melanoma patients with LMD and used as preclinical models. These models retained melanoma expression patterns and had signaling pathways that are therapeutically targetable. These novel models/reagents may be useful in developing rationally designed treatments for LMD.

show abstract

“…A case report of LMD in a patient with uveal melanoma demonstrates the ability to identify and quantify CSF-CTCs based on an anti-high-molecular-weight melanoma-associated antigen-positive and CD45/CD34-negative staining pattern using the Veridex Cell-Search platform (Fedorenko et al, 2016). The largest study utilizing quantification of CSF-CTCs using the CellSearch platform for the diagnosis of LMD from epithelial tumors demonstrated a sensitivity of 93%, specificity of 95%, positive predictive value 90%, and negative predictive value 97% using the EPCAM+ and CD45-negative 1 CSF-CTC/mL cutoff (Lin et al, 2017).…”

Section: Circulating Tumor Cellsmentioning

confidence: 99%

“…Prompt diagnosis of LMD is critical in order to initiate therapy, hence reliable tools to assist with diagnosis can potentially improve outcome. As such, several liquid biopsy approaches are currently being developed to aid in LMD diagnosis and to interrogate the biology of the disease, including the quantification of circulating tumor cells (CTCs) and the assessment of cell‐free (cf)DNA in the CSF (Bale et al, 2021; Fedorenko et al, 2016; Li et al, 2016; Lin et al, 2017; Melms et al, 2018; Smalley et al, 2020; Wijetunga et al, 2021).…”

Section: The Current State Of Diagnosis and Prognosismentioning

confidence: 99%

Leptomeningeal disease in melanoma: An update on the developments in pathophysiology and clinical care

Smalley,

Boire,

Brastianos

et al. 2023

Pigment Cell Melanoma Res

Self Cite

View full text Add to dashboard Cite

Leptomeningeal disease (LMD) remains a major challenge in the clinical management of metastatic melanoma patients. Outcomes for patient remain poor, and patients with LMD continue to be excluded from almost all clinical trials. However, recent trials have demonstrated the feasibility of conducting prospective clinical trials in these patients. Further, new insights into the pathophysiology of LMD are identifying rational new therapeutic strategies. Here we present recent advances in the understanding of, and treatment options for, LMD from metastatic melanoma. We also annotate key areas of future focus to accelerate progress for this challenging but emerging field.

show abstract

A rare case of leptomeningeal carcinomatosis in a patient with uveal melanoma: case report and review of literature

Cited by 10 publications

References 43 publications

Leptomeningeal Disease (LMD) in Patients with Melanoma Metastases

Leptomeningeal Disease (LMD) in Patients with Melanoma Metastases

A preclinical model of patient-derived cerebrospinal fluid circulating tumor cells for experimental therapeutics in leptomeningeal disease from melanoma

Leptomeningeal disease in melanoma: An update on the developments in pathophysiology and clinical care

Contact Info

Product

Resources

About