Hemorrhagic Brain Metastases: A Diagnostic Dilemma and Diagnosis of Exclusion

Pleomorphic carcinoma is a malignant and aggressive primary lung carcinoma that occurs at a rate of approximately 0.3%. This rarely encountered tumor may present a diagnostic challenge to neuroradiologists and pathologists, as it has propensity to present as hemorrhagic brain metastasis with unknown primary and result in delay in diagnosis that could impact clinical outcome. Herein, we report a unique case in its presentation in a 56-year-old female, having symptomatic brain metastasis prior to the discovery of the pulmonary lesion.

Case Report: Primary Pulmonary Angiosarcoma With Brain Metastasis

Primary pulmonary angiosarcoma (PPA) is a rare malignant vascular tumor, of which early diagnosis is challenging due to lack of specific clinical manifestations and a low level of suspicion. Here, we report a case of PPA presented with advanced brain metastasis. A 21-year-old patient with 1 week history of headache and mild cough was hospitalized for a head injury. Head MRI showed multiple intracranial lesions with brain edema. Chest CT displayed bilateral pulmonary infiltrates with mediastinal lymph node enlargement. After 2 months of anti-tuberculosis treatment, the patient was readmitted for persistent headache and cough with occasional hemosputum along with worsening pulmonary and intracranial lesions. Despite seizure prophylaxis and control of intracranial pressure and brain edema, his symptoms progressively aggravated, accompanied by cough with bloody sputum, frequent epileptic seizures, and hypotension. He eventually developed coma and died within 3 months of onset of symptoms. An autopsy confirmed PPA with brain metastasis.

Metabolic Reprogramming Underlying Brain Metastasis of Breast Cancer

The development of brain metastasis is a major cause of death in patients with breast cancer, characterized by rapid progression of the disease and poor prognosis, and lack of effective treatment has existed as an unresolved issue clinically. Extensive research has shown that a variety of metabolic changes associated with cellular metastasis exist in primary breast cancer or brain metastases, therefore to elucidate metabolic characteristics at each step of the metastasis cascade will provide important clues to the efficient treatment. In this review, we discuss the changes in metabolic patterns of breast cancer cells at every step of metastasis for exploring the potential therapeutic target based on metabolic reprogramming, and provide new insights on the design and development of drugs for breast cancer brain metastasis.

Interaction of Glia Cells with Glioblastoma and Melanoma Cells under the Influence of Phytocannabinoids

Brain tumor heterogeneity and progression are subject to complex interactions between tumor cells and their microenvironment. Glioblastoma and brain metastasis can contain 30–40% of tumor-associated macrophages, microglia, and astrocytes, affecting migration, proliferation, and apoptosis. Here, we analyzed interactions between glial cells and LN229 glioblastoma or A375 melanoma cells in the context of motility and cell–cell interactions in a 3D model. Furthermore, the effects of phytocannabinoids, cannabidiol (CBD), tetrahydrocannabidiol (THC), or their co-application were analyzed. Co-culture of tumor cells with glial cells had little effect on 3D spheroid formation, while treatment with cannabinoids led to significantly larger spheroids. The addition of astrocytes blocked cannabinoid-induced effects. None of the interventions affected cell death. Furthermore, glial cell-conditioned media led to a significant slowdown in collective, but not single-cell migration speed. Taken together, glial cells in glioblastoma and brain metastasis micromilieu impact the tumor spheroid formation, cell spreading, and motility. Since the size of spheroid remained unaffected in glial cell tumor co-cultures, phytocannabinoids increased the size of spheroids without any effects on migration. This aspect might be of relevance since phytocannabinoids are frequently used in tumor therapy for side effects.