Glioblastoma multiforme (GBM) is characterized by its infiltrative growth pattern and high recurrence rate despite treatment. While local progression within the central nervous system (CNS) is the rule, manifestations outside the CNS, particularly skin and subcutaneous metastases, are very infrequent and seldom reported in the literature. The authors reviewed the current understanding of this rare condition, with the main purpose of giving visibility to its clinical presentation and prognostic implications, thus improving clinical management and encouraging research in this area. A PubMed, Cochrane Library, and EMBASE search from database inception through March 2024 was conducted. In this way, we compiled a total of thirty-five cases in our review. As far as we know, our work gathers the largest number of patients with this condition. Remarkably, we observed that the typical presentation of soft-tissue high-grade glioma metastases is the finding of subcutaneous erythematous nodules in patients previously operated on for a primary CNS tumor, within the craniotomy site and nearby, mostly in the first year after the initial surgery. It was also noted that there is a trend of developing a concomitant CNS recurrence and/or other metastases in different locations, either simultaneously or subsequently. From here, we propose some possible mechanisms that explain the extracranial spread of GBM. We concluded that a poor outcome is expected from the diagnosis of skin and subcutaneous metastases: the mean overall survival was 4.38 months. Yet, assessing individual characteristics is always mandatory; a palliative approach seems to be the best option for the majority of cases.

Glioblastoma multiforme (GBM) is the most common malignant primary central nervous system (CNS) tumor. It presents an aggressive pattern, with a tendency for intracranial progression despite optimal treatment. On the other hand, metastases and manifestations outside the CNS are exceptional, and very few cases have been described. The authors submitted a case of a 48-year-old male diagnosed with a left parietooccipital GBM isocitrate dehydrogenase (IDH) wild-type, non-methylated O⁶-methylguanine-DNA methyltransferase (MGMT). Six months after surgical treatment, followed by a chemotherapy (CT) and radiotherapy scheme, he developed a few subcutaneous erythematous nodules within the surgical scar. A punch biopsy confirmed the histopathology of GBM. The CT scan showed concomitant intracranial progression. We ruled out systemic metastases. As the performance status was good [Karnofsky Performance Status 90 (KPS 90)] and the subcutaneous implants were growing rapidly, limiting the quality of life, we decided to perform palliative surgery to remove the implants. The result was good. Unfortunately, the patient worsened during the following week, after ruling out medical complications, we attributed the worsening to cerebral tumor swelling, revealed in the CT scan, as unresponsive to steroids. He passed away a few days later. Based on the analysis of our case, we intend to provide useful information for the approach to this peculiar manifestation of GBM.

Brain metastasis is the most prevalent neurologic problem of systemic cancer and it can increase the mortality rate in patients with cancer. It occurs more in patients with lung cancer, breast cancer, and melanoma. There are several molecular mechanisms in cancer cell progression, invasion, and location in new places during brain metastasis. Significant interactions between cancer cells, the brain microenvironment, and the blood-brain barrier (BBB) play a major role in brain metastasis. This study will focus on molecular mechanisms that contribute to cancer metastasis into the brain and finding new treatments with molecular research. Treatment strategies in patients with brain metastasis include surgical resection, radiotherapy, and chemotherapy; however, the penetration of chemotherapy drugs beyond the BBB is limited. Studying molecular, cellular, and physical mechanisms in brain metastasis helps to improve new strategies in drug delivery across the BBB. There are significant impacts of ion channels in brain metastasis and cancer treatment failure. Targeting molecular mechanisms and ion channels in brain metastasis led to increasing the better response in these patients. In this way, nano-drugs have caused a revolution in effective targeting and drug delivery in cancer treatment. This review describes the advances to facilitate the penetration of drugs in the BBB by using nano-drugs especially those that are targeting ion channels.