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Journal of Cancer Research and... 2022Parameningeal rhabdomyosarcomas (PM RMSs) are rarely seen childhood tumors. Their treatment might be challenging and prognosis is poor compared to other head and neck... (Review)
Review
Parameningeal rhabdomyosarcomas (PM RMSs) are rarely seen childhood tumors. Their treatment might be challenging and prognosis is poor compared to other head and neck RMS. Here we report a PM RMS presenting with leptomeningeal seeding metastasis a year after diagnosis. A five-year-old girl presented with an enlarging mass protruding from the right ear and right facial paralysis. Magnetic resonance imaging (MRI) revealed a large mass extending from right external auditory canal to the temporal lobe, pterygoid fossa and nasopharynx with an intracranial component indenting the right temporal lobe and extending into the right cavernous sinus. Trucut biopsy revealed embryonal rhabdomyosarcoma. Cerebrospinal fluid (CSF) cytology was negative for malignant cells. Chemotherapy was started since it was found unresectable. At second week of chemotherapy, radiotherapy was applied to primary tumor location with intensity-modulated radiation therapy (IMRT) technique in 1.8 Gy fractions to total dose of 50.4 Gy. At week 27, MRI showed significant response. At week 36, the patient presented with vomiting and tendency to sleep. MRI was found to be compatible with meningitis and antibacterial therapy was started. At week 39, chemotherapy was stopped. But MRI performed one month later revealed linear contrast enhancements around the spinal cord compatible with leptomeningeal metastases. Chemotherapy and craniospinal irradiation were applied. But the patient did not improve and received palliative treatment. Six months after the completion of radiotherapy the patient died. Treatment of parameningeal rhabdomyosarcomas require multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Prognosis is poor for patients with leptomeningeal spread.
Topics: Female; Humans; Child; Child, Preschool; Rhabdomyosarcoma, Embryonal; Rhabdomyosarcoma; Meningeal Carcinomatosis; Meninges; Magnetic Resonance Imaging
PubMed: 36412455
DOI: 10.4103/jcrt.JCRT_1491_20 -
Neurology India 2022Spinal dural arteriovenous fistulae (SDAVF) are most commonly idiopathic in origin but may occasionally be seen secondary to surgery, trauma, or inflammation. We report...
Spinal dural arteriovenous fistulae (SDAVF) are most commonly idiopathic in origin but may occasionally be seen secondary to surgery, trauma, or inflammation. We report a case of 27-year-old male who came with features of a myelopathy. He was found to have an SDAVF associated with leptomeningeal spread (LMS) of a previously treated high-grade cerebral glioma. Hemorrhagic presentation of gliomas, as in this case, is due to upregulation of vascular endothelial growth factor, which has also been postulated to play a role in the development of SDAVFs. This may suggest a possible mechanism of induction of secondary SDAVFs associated with such tumors. While the coexistence of intracranial neoplasms with vascular malformations has been reported previously, this is the first case report of LMS of a high-grade glioma associated with an SDAVF.
Topics: Adult; Humans; Male; Brain Neoplasms; Central Nervous System Vascular Malformations; Glioma; Magnetic Resonance Imaging; Meningeal Carcinomatosis; Spinal Cord Diseases; Vascular Endothelial Growth Factor A; Dura Mater; Neoplasm Invasiveness
PubMed: 36412391
DOI: 10.4103/0028-3886.360935 -
American Journal of Ophthalmology Case... Dec 2022To present a rare case of advanced disseminated prostate cancer with bilateral visual loss as the initial manifestation of the disease.
PURPOSE
To present a rare case of advanced disseminated prostate cancer with bilateral visual loss as the initial manifestation of the disease.
OBSERVATIONS
A 55-year-old man referring progressive visual blurring for the last 6 months and painless severe bilateral visual loss in the last 7 days prior to our consultation, associated with a bilateral optic disc swelling and leptomeningeal metastases from a previously ignored prostate carcinoma is presented. Rapid improvement of visual acuity and involution of leptomeningeal metastasis was observed after initiation of the specific oncologic treatment.
CONCLUSIONS AND IMPORTANCE
Bilateral visual loss may be the initial manifestation of leptomeningeal carcinomatosis from an ignored prostate cancer. Prompt diagnosis is crucial in order to improve the quality of life of a critically ill patient with a disseminated prostate cancer.
PubMed: 36393904
DOI: 10.1016/j.ajoc.2022.101748 -
BMC Neurology Nov 2022Meningeal carcinomatosis is mainly associated with breast cancer, lung cancer, and melanoma. However, meningeal carcinomatosis secondary to a neurenteric cyst with...
BACKGROUND
Meningeal carcinomatosis is mainly associated with breast cancer, lung cancer, and melanoma. However, meningeal carcinomatosis secondary to a neurenteric cyst with malignant features is extremely rare.
CASE PRESENTATION
We report the case of a 35-year-old woman who was admitted to the hospital with a 10-month history of headache, 6-month history of diplopia, 4-month history of hearing loss, and 1-month history of back pain, suggesting a diagnosis of chronic meningitis. Notably, enhanced brain and spinal cord magnetic resonance imaging (MRI) revealed extensive lesions with enhancement signals in the pia mater of the pons and cervical, thoracic, and lumbar spinal cord. The cerebral spinal fluid profile showed that pressure was significantly elevated, with a slight increase in leukocytes that mostly comprised mononuclear cells and decreased glucose concentration. Cytology evaluation showed a small cluster of atypical nuclei, which were suspected to be tumor cells arising from the epithelium. However, no primary tumor was found through comprehensive body and skin screening. After a histopathological biopsy of subarachnoid meninx of the thoracic spinal canal, the cause of meningeal carcinomatosis of this patient was determined as neurenteric cysts with malignant features, which is extremely rare.
CONCLUSION
This is the first case to ever report neurenteric cysts as a cause of leptomeningeal carcinomatosis and the first ever report of neurenteric cysts presenting as leptomeningeal carcinomatosis without typical cyst visible on brain MRI. This extremely rare case provided a novel view on the pathogenesis of meningeal carcinomatosis and clinical presentation of neurenteric cysts, highlighting the value of meningeal biopsy in chronic meningitis of unknown causes.
Topics: Female; Humans; Adult; Meningeal Carcinomatosis; Neural Tube Defects; Cell Transformation, Neoplastic; Magnetic Resonance Imaging; Spinal Cord Diseases; Meningitis
PubMed: 36384561
DOI: 10.1186/s12883-022-02978-7 -
Journal of the Egyptian National Cancer... Nov 2022The reported incidence of leptomeningeal carcinomatosis is 3-8% in patients with solid tumours. More commonly, it has been described in the setting of advanced cancers...
BACKGROUND
The reported incidence of leptomeningeal carcinomatosis is 3-8% in patients with solid tumours. More commonly, it has been described in the setting of advanced cancers of the lung, breast and malignant melanoma.
CASE PRESENTATION
A 50-year-old diabetic patient with recurrent unresectable squamous cell carcinoma (SCC) of the right retromolar trigone (rT4bN0M0) presented with severe low backache and weakness in bilateral lower limbs 20 days after the completion of concurrent chemoradiotherapy. Contrast-enhanced MRI of the spine showed multiple nodular enhancing leptomeningeal lesions at the lumbar level and an intramedullary T2/FLAIR-hyperintense longitudinal lesion involving the central cord from C2 to C7 vertebral levels, suggestive of leptomeningeal metastases. Cerebrospinal fluid (CSF) analysis revealed pleocytosis, elevated protein and markedly decreased glucose. The CSF cytology revealed scattered large atypical cells, suspicious for metastasis. Non-contrast MRI of the brain showed a T2/FLAIR-hyperintense lesion involving the right caudate nucleus suggestive of either an acute infarct with haemorrhagic transformation or a haemorrhagic brain metastasis. During assessment, he had high-grade fever and was started on empirical intravenous antibiotics (ceftriaxone, vancomycin and subsequently meropenem) in line with the management for acute bacterial meningitis. Gram staining of CSF did not demonstrate the presence of any bacteria and the specimen was sterile on culture. He did not respond to empirical antibiotics, had a progressive downhill course and eventually died due to aspiration pneumonia.
CONCLUSION
This brief report highlights the importance of awareness of leptomeningeal carcinomatosis as a possible cause of backache with sensorimotor deficit and autonomic dysfunction in a previously treated case of head and neck SCC.
Topics: Male; Humans; Middle Aged; Meningeal Carcinomatosis; Neoplasm Recurrence, Local; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Anti-Bacterial Agents
PubMed: 36336772
DOI: 10.1186/s43046-022-00147-y -
Cancer Medicine Feb 2023Leptomeningeal metastasis (LM) refers to the dissemination of malignant cells in the subarachnoid space, pia, and arachnoid mater and is a severe condition associated... (Review)
Review
Leptomeningeal metastasis (LM) refers to the dissemination of malignant cells in the subarachnoid space, pia, and arachnoid mater and is a severe condition associated with metastatic solid tumors. The most common solid tumor that develops into LM is lung cancer and the incidence increased in patients with advanced non-small-cell lung cancer (NSCLC) with targetable mutations. However, tissue biopsy of LM is inaccessible, leading to the paucity of genomic profiles of LM to guide targeted treatments and explore biological mechanisms. In recent years, liquid biopsy is considered a minimally invasive and dynamic method to trace the genomic alterations of cancer cells and some studies started to perform sequencing of cerebrospinal fluid (CSF) in patients with LM to reveal the targeted mutations and genomic profiles. In this review, we focused on studies performed sequencing of CSF in NSCLC patients with LM and summarized the sequencing results and their commonality. As the only way to reveal the genomic landscapes of LM, our review provided evidence that sequencing of CSF is a promising management method in LM patients to dynamically guide target therapy and monitor intracranial tumor response. Furthermore, it reveals a unique genomic profile of LM including driver genes, drug-resistant mutations, and a number of copy number variations. Sequencing of CSF in LM patients seems to provide more comprehensive genomic information than we expected and the biological significance behind the genomic alternations needs further study.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; DNA Copy Number Variations; Meningeal Carcinomatosis; Mutation
PubMed: 36000927
DOI: 10.1002/cam4.5163 -
Neuro-oncology Mar 2023Patients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately...
A phase I/II study of intrathecal trastuzumab in human epidermal growth factor receptor 2-positive (HER2-positive) cancer with leptomeningeal metastases: Safety, efficacy, and cerebrospinal fluid pharmacokinetics.
BACKGROUND
Patients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum-tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive leptomeningeal disease (LMD).
METHODS
This multicenter study enrolled 34 LMD patients in a combined phase I/II study in treating patients with intrathecal trastuzumab. Any HER2-positive histology was allowed in the phase I; the phase II was limited to HER2-positive breast cancer.
RESULTS
Intrathecal trastuzumab was well-tolerated, with one dose limiting toxicity of grade 4 (arachnoiditis) occurring at the 80 mg twice weekly dose. The recommended phase II dose was 80 mg intrathecally twice weekly. Twenty-six patients at dose level 80 mg were included in evaluation for efficacy: partial response was seen in 5 (19.2%) patients, stable disease was observed in 13 (50.0%), and 8 (30.8%) of the patients had progressive disease. Median overall survival (OS) for phase II dose treated patients was 8.3 months (95% CI 5.2-19.6). The phase II HER2-positive breast cancer patients median OS was 10.5 months (95% CI 5.2-20.9). Pharmacokinetic (PK) studies were limited in the setting of concurrent systemic trastuzumab administration, however, did show stable cerebrospinal fluid (CSF) concentrations with repeated dosing suggest that trastuzumab does not accumulate in the CSF in toxic concentrations.
CONCLUSION
This study suggests promise for potentially improved outcomes of HER-positive LMD patients when treated with intrathecal trastuzumab while remaining safe and well-tolerated for patients.
Topics: Humans; Female; Trastuzumab; Receptor, ErbB-2; Breast Neoplasms; Meningeal Carcinomatosis; Antineoplastic Combined Chemotherapy Protocols
PubMed: 35948282
DOI: 10.1093/neuonc/noac195 -
Zhongguo Fei Ai Za Zhi = Chinese... Jul 2022Leptomeningeal metastases (LM), a special type of metastasis in advanced lung cancer, is known for its severe clinical symptoms, rapid progression and poor prognosis. LM... (Review)
Review
Leptomeningeal metastases (LM), a special type of metastasis in advanced lung cancer, is known for its severe clinical symptoms, rapid progression and poor prognosis. LM used to be featured with low clinical diagnosis rate, limited treatment options, poor treatment efficacy, and very short survival if treatment not given. Though cerebrospinal fluid (CSF) cytology remains to be the gold standard for the diagnosis of LM, the positive rate of the first CSF cytology even in patients with suggestive clinical symptoms and positive imaging generally does not exceed 50%, leading to a delay in the diagnosis and treatment of patients with LM. With the progress of targeted therapy for driver gene-positive lung cancer and immunotherapy for driver gene-negative lung cancer, the overall survival of patients with lung cancer has been prolonged, meanwhile incidence of LM has been increasing year by year. Current clinical research in this field center around how to improve diagnosis rate and to find effective treatment approaches. This paper reviews advances in diagnosis and treatment of LM of lung cancer.. .
Topics: Humans; Lung Neoplasms; Meningeal Carcinomatosis; Meningeal Neoplasms; Treatment Outcome
PubMed: 35899451
DOI: 10.3779/j.issn.1009-3419.2022.102.25 -
Thoracic Cancer Sep 2022The prognosis of non-small-cell lung cancer (NSCLC) with leptomeningeal metastasis (LM) is poor. Detection of cell-free DNA (cfDNA) by next generation sequencing (NGS)...
BACKGROUND
The prognosis of non-small-cell lung cancer (NSCLC) with leptomeningeal metastasis (LM) is poor. Detection of cell-free DNA (cfDNA) by next generation sequencing (NGS) in cerebrospinal fluid (CSF) may facilitate diagnosis of LM and identification of drug resistance mechanisms, yet its clinical use needs to be further verified.
METHODS
We performed a retrospective cohort study to assess the genetic profiles of paired CSF and plasma samples in lung cancer patients with LM. Of 17 patients screened, a total of 14 patients with LM and paired NGS tests were enrolled.
RESULTS
All patients harbor driver gene mutations, including 12 epidermal growth factor receptor (EGFR) activating mutations, 1 anaplastic lymphoma kinase (ALK) rearrangement, and 1 ROS-1 fusion. Genetic mutations were detected in CSF cfDNA from 92.9% patients (13/14), which was significantly higher than that from the plasma (9/14, 64.2%). The mutations were highly divergent between CSF and plasma cfDNA, with a concordance rate of 24.38% and 10 mutations shared by the two media. CSF cfDNA could also benefit the analysis of resistance mechanisms to targeted therapies. In five patients who experienced progression on 1st or 2nd generation EGFR-tyrosine kinase inhibitors (TKIs), RB1 mutation, and amplification of MET and EGFR were detected in CSF cfDNA only. In eight patients with LM progression on osimertinib resistance, EGFR amplification was detected in CSF cfDNA from four patients, whereas no CNVs were detected in the matched plasma samples.
CONCLUSIONS
In conclusion, CSF could be superior to plasma in providing a more comprehensive genetic landscape of LM to find out drug resistance mechanisms and guide subsequent treatments.
Topics: Carcinoma, Non-Small-Cell Lung; Cell-Free Nucleic Acids; ErbB Receptors; Genotype; Humans; Lung Neoplasms; Meningeal Carcinomatosis; Mutation; Protein Kinase Inhibitors; Retrospective Studies
PubMed: 35896160
DOI: 10.1111/1759-7714.14592 -
Neuro-oncology Feb 2023Patients with HER2-positive breast cancer (HER2 + BC) develop central nervous system metastases twice as often as patients with luminal HER2-negative breast cancer....
BACKGROUND
Patients with HER2-positive breast cancer (HER2 + BC) develop central nervous system metastases twice as often as patients with luminal HER2-negative breast cancer. Leptomeningeal progression results in a drastically altered prognosis with limited therapeutic options. This phase II study was conducted to assess the efficacy of intrathecal (IT) trastuzumab in HER2 + BC patients with leptomeningeal metastasis (LM), based on a phase I dose-escalation study that had determined the recommended weekly dose of 150 mg for phase II.
METHODS
Eligible patients received weekly administrations of 150 mg of IT trastuzumab. The primary endpoint was clinical neurologic progression-free survival (LM-related-PFS) after 8 weeks. Overall survival (OS), toxicities, and quality of life (QoL) were secondary endpoints.
RESULTS
Among the 19 enrolled patients, 16 (84%) had concomitant brain metastases, 15 of them had received prior radiotherapy to the brain. All patients had received at least one line of systemic anti-HER2 therapy. After 8 weeks, 14 patients (74%) were free of neurological progression. The median LM-related-PFS was 5.9 months and the median OS was 7.9 months. According to the QLQ-C30 and BN20 scales, the global health-related QoL status seemed preserved and no toxicity above grade 3 was observed.
CONCLUSIONS
Conducting studies on patients with LM poses significant challenges and ethical dilemmas inherent to this population. Despite some limits, this phase II study's findings in terms of clinical neurologic response and QoL's control confirms weekly administration of 150 mg of IT trastuzumab as a valuable option for HER + BC patients with LM and support the interest for further investigations.
Topics: Humans; Female; Trastuzumab; Breast Neoplasms; Quality of Life; Receptor, ErbB-2; Meningeal Carcinomatosis; Antineoplastic Combined Chemotherapy Protocols
PubMed: 35868630
DOI: 10.1093/neuonc/noac180