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Cancer Reports (Hoboken, N.J.) Apr 2022Leptomeningeal metastasis (LM), or spread of cancer cells into the cerebrospinal fluid (CSF), is characterized by a rapid onset of debilitating neurological symptoms and...
BACKGROUND
Leptomeningeal metastasis (LM), or spread of cancer cells into the cerebrospinal fluid (CSF), is characterized by a rapid onset of debilitating neurological symptoms and markedly bleak prognosis. The lack of reproducible in vitro and in vivo models has prevented the development of novel, LM-specific therapies. Although LM allows for longitudinal sampling of floating cancer cells with a spinal tap, attempts to culture patient-derived leptomeningeal cancer cells have not been successful.
AIM
We, therefore, employ leptomeningeal derivatives of human breast and lung cancer cell lines that reproduce both floating and adherent phenotypes of human LM in vivo and in vitro.
METHODS AND RESULTS
We introduce a trypsin/EDTA-based fractionation method to reliably separate the two cell subsets and demonstrate that in vitro cultured floating cells have decreased proliferation rate, lower ATP content, and are enriched in distinct metabolic signatures. Long-term fractionation and transcriptomic analysis suggest high degree plasticity between the two phenotypes in vitro. Floating cells colonize mouse leptomeninges more rapidly and associate with shortened survival. In addition, patients harboring LM diagnosed with CSF disease alone succumbed to the disease earlier than patients with adherent (MRI positive) disease.
CONCLUSION
Together, these data support mechanistic evidence of a metabolic adaptation that allows cancer cells to thrive in their natural environment but leads to death in vitro.
Topics: Animals; Biomarkers, Tumor; Cell Line, Tumor; Humans; Lung Neoplasms; Meningeal Carcinomatosis; Mice; Phenotype
PubMed: 33372403
DOI: 10.1002/cnr2.1236 -
European Journal of Radiology Feb 2024The purpose of this study is to investigate whether the presence and pattern of enhancement at the internal acoustic canal (IAC) could help in discriminating between...
PURPOSE
The purpose of this study is to investigate whether the presence and pattern of enhancement at the internal acoustic canal (IAC) could help in discriminating between leptomeningeal carcinomatosis (LCa) and meningeal inflammation/infection (MMI).
METHODS
Magnetic resonance (MR) images of patients with leptomeningeal enhancement were retrospectively evaluated. MR images of the LCa group (n = 33), MMI group (n = 19) and control group (n = 33) were evaluated for the presence, type (moderate/prominent), and localization (unilateral/bilateral) of the IAC enhancement.
RESULTS
The presence of IAC enhancement was significantly more common in patients with LCa (p < 0.001). In 73.7 % of patients with MMI, no contrast enhancement was observed in the IAC. In patients with contrast enhancement in the IAC, the risk of LCa in the etiology is 20 times greater than the risk of having MMI. Seventy-five percent of the IAC enhancement seen in LCa patients and 20 % of the IAC enhancements seen in MMI patients was bilateral. This difference was statistically significant (p = 0.029).
CONCLUSION
Intense contrast enhancement of the IAC can be a marker for LCa.
Topics: Humans; Meningeal Carcinomatosis; Retrospective Studies; Meninges; Inflammation; Magnetic Resonance Imaging
PubMed: 38237519
DOI: 10.1016/j.ejrad.2024.111299 -
Acta Cytologica 2017Meningeal carcinomatosis (MC) is a rare complication in breast cancer patients. It is defined as a diffuse or multifocal leptomeningeal metastasis.
OBJECTIVE
Meningeal carcinomatosis (MC) is a rare complication in breast cancer patients. It is defined as a diffuse or multifocal leptomeningeal metastasis.
STUDY DESIGN
From our institution database, we retrospectively studied 19 patients diagnosed with MC in the cerebrospinal fluid (CSF) in 1997-2015, in order to evaluate tumor prognostic markers, histologic subtypes, and clinical outcome.
RESULTS
All patients were female, with a mean age of 53 years (range 36-75 years). The mean interval between diagnosis of breast carcinoma and MC was 28 months (range 6-62 months). The median survival from the time of diagnosis was 2 months (1-51 months). Sixteen cases (84%) were the ductal phenotype, 62% of which were of a high grade (grade 3), and 3 cases (16%) were lobular. Estrogen and progesterone receptors were positive on immunohistochemistry (IHC) in 53 and 33% of patients, respectively. HER2 IHC was positive (3+) in 20% of the cases; all were amplified by fluorescence in situ hybridization. The incidence of MC in triple-negative tumors was 40%. Twelve patients (63%) already had known metastasis at the time of diagnosis.
CONCLUSIONS
Most cases of MC are high-grade ductal. MC is more common in triple-negative breast cancers. The outcome of these breast cancer patients with MC was poor. There was no survival difference according to age, histologic subtype, grade, or hormonal or HER2 status.
Topics: Adult; Aged; Biomarkers, Tumor; Biopsy; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Databases, Factual; Female; Humans; Illinois; Immunohistochemistry; In Situ Hybridization, Fluorescence; Meningeal Carcinomatosis; Middle Aged; Neoplasm Grading; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Survival Analysis; Time Factors; Triple Negative Breast Neoplasms
PubMed: 28231581
DOI: 10.1159/000455115 -
Current Oncology (Toronto, Ont.) Aug 2021Sensorineural hearing loss (SNHL) has been reported rarely in patients with meningeal carcinomatosis (MC). We summarized the clinical data of eight MC patients with SNHL...
Sensorineural hearing loss (SNHL) has been reported rarely in patients with meningeal carcinomatosis (MC). We summarized the clinical data of eight MC patients with SNHL and 35 patients reported from publications. In the eight patients with SNHL, the medium onset age was 48 (range from 37 to 66) years and six (75%) were male. Seven (87.5%) suffered from headaches as the initial symptom, and they experienced SNHL during the first two months after the occurrence of headaches (0.5 to 2 months, average 1.5 months). The audiogram configuration was flat in three patients (37.5%) and showed total deafness in five patients (62.5%). The damage of cranial nerves VI (abducens) was observed in six patients (75%), and four patients (50%) had cranial nerves VII (facial) injury during the disease course. The percentage of damage of cranial nerves was higher than the patients without SNHL (VIth, 75.0% vs. 13.3%, = 0.002 and VIIth 50.0% vs. 6.7%, = 0.012). Four (50%) patients suffered from lung adenocarcinoma as primary tumor, two (25%) experienced stomach adenocarcinoma, one had colon cancer, and one patient was unknown. The symptom of SNHL improved after individualized therapy in four patients (focal radiotherapy and chemotherapy for three patients and whole brain radiotherapy for one patient), but all passed away from 2 to 11 months after diagnosis. Total deafness and flat hearing loss in audiogram were the common types of SNHL resulting from MC. MC patients with SNHL were more likely to suffer from the damage of other cranial nerves, especially to cranial nerves VI and VII. Treatment might improve SNHL, but not improve the case fatality rate.
Topics: Adenocarcinoma; Adult; Aged; Deafness; Disease Progression; Hearing Loss, Sensorineural; Humans; Male; Meningeal Carcinomatosis; Middle Aged
PubMed: 34449589
DOI: 10.3390/curroncol28050281 -
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 -
Neuro-oncology Mar 2019Leptomeningeal metastases (LM) in breast cancer patients are rare but often accompanied by devastating neurological symptoms and carry a very poor prognosis, even if... (Review)
Review
Leptomeningeal metastases (LM) in breast cancer patients are rare but often accompanied by devastating neurological symptoms and carry a very poor prognosis, even if treated. To date, two diagnostic methods are clinically used to diagnose LM: gadolinium MRI of the brain and/or spinal cord and cytological examination of cerebrospinal fluid (CSF). Both techniques are, however, hampered by limited sensitivities, often leading to a long diagnostic process requiring repeated lumbar punctures and MRI examinations. To improve the detection rate of LM, numerous studies have assessed new techniques. In this review, we present the current workup to diagnose LM, set out an overview of novel techniques to diagnose LM, and give recommendations for future research.
Topics: Breast Neoplasms; Female; Humans; Meningeal Carcinomatosis
PubMed: 30418595
DOI: 10.1093/neuonc/noy186 -
BMC Cancer Dec 2015The incidence of meningeal carcinomatosis appears to be higher than in the past due to advances in neuro-imaging diagnostic techniques and improvements in cancer...
BACKGROUND
The incidence of meningeal carcinomatosis appears to be higher than in the past due to advances in neuro-imaging diagnostic techniques and improvements in cancer survival. Among solid tumors, breast cancer is the cancer most commonly associated with meningeal carcinomatosis, with an incidence rate of between 0.8 and 16%. Aim of this study has been i) to evaluate the incidence of meningeal carcinomatosis in a continuous breast cancer unselected series treated in a dedicated Breast Unit and ii) to define the clinico-pathological and molecular parameters associated with meningeal carcinomatosis development.
METHODS
A retrospective series of 1915 consecutive patients surgically treated for breast cancer between 1998 and 2010 was collected. Clinico-pathological data were recorded from medical charts and pathological reports, including the date of development of symptomatic meningeal carcinomatosis. Meningeal carcinomatosis incidence was determined at both 5- and 10-year follow-ups.
RESULTS
Three patients in the first 5 years of follow-up and six patients in 10 years of follow-up developed meningeal carcinomatosis. An incidence rate of 5.44 per 10,000 patients (95% CI: 1.75-16.9) was observed, with a 5-year risk of 0.3%. At 10-year follow up, the rate increased to 7.55 per 10,000 patients (95% CI: 3.39-16.8). In a univariate analysis, young age, tumor size larger than 15 mm, histological grade 3, more than three metastatic lymph nodes, negative estrogen receptor, positive HER2 and high proliferative index were significantly associated with meningeal carcinomatosis development.
CONCLUSIONS
In an unselected breast cancer population, meningeal carcinomatosis is a rare event that is associated with adverse prognostic factors. Meningeal carcinomatosis incidence is overestimated when recorded in biased/high-risk selected breast cancer patients and should not be considered to accurately reflect the overall breast cancer population.
Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Female; Humans; Incidence; Meningeal Carcinomatosis; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Young Adult
PubMed: 26715407
DOI: 10.1186/s12885-015-2042-y -
Nature Reviews. Clinical Oncology Sep 2022
Topics: Craniospinal Irradiation; Humans; Meningeal Carcinomatosis; Treatment Outcome
PubMed: 35882997
DOI: 10.1038/s41571-022-00669-3 -
Strahlentherapie Und Onkologie : Organ... Apr 2024The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of... (Review)
Review
PURPOSE
The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of radiotherapy for brain metastases and leptomeningeal carcinomatosis.
MATERIALS AND METHODS
For the current review, a PubMed search was conducted including articles from 01/1985 to 05/2023. The search was performed using the following terms: (brain metastases OR leptomeningeal carcinomatosis) AND (breast cancer OR breast) AND (radiotherapy OR ablative radiotherapy OR radiosurgery OR stereotactic OR radiation).
CONCLUSION AND RECOMMENDATIONS
Despite the fact that the biological subtype of breast cancer influences both the occurrence and relapse patterns of breast cancer brain metastases (BCBM), for most scenarios, no specific recommendations regarding radiotherapy can be made based on the existing evidence. For a limited number of BCBM (1-4), stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT) is generally recommended irrespective of molecular subtype and concurrent/planned systemic therapy. In patients with 5-10 oligo-brain metastases, these techniques can also be conditionally recommended. For multiple, especially symptomatic BCBM, whole-brain radiotherapy (WBRT), if possible with hippocampal sparing, is recommended. In cases of multiple asymptomatic BCBM (≥ 5), if SRS/SRT is not feasible or in disseminated brain metastases (> 10), postponing WBRT with early reassessment and reevaluation of local treatment options (8-12 weeks) may be discussed if a HER2/Neu-targeting systemic therapy with significant response rates in the central nervous system (CNS) is being used. In symptomatic leptomeningeal carcinomatosis, local radiotherapy (WBRT or local spinal irradiation) should be performed in addition to systemic therapy. In patients with disseminated leptomeningeal carcinomatosis in good clinical condition and with only limited or stable extra-CNS disease, craniospinal irradiation (CSI) may be considered. Data regarding the toxicity of combining systemic therapies with cranial and spinal radiotherapy are sparse. Therefore, no clear recommendations can be given, and each case should be discussed individually in an interdisciplinary setting.
Topics: Humans; Female; Meningeal Carcinomatosis; Breast Neoplasms; Cranial Irradiation; Neoplasm Recurrence, Local; Brain Neoplasms; Radiosurgery
PubMed: 38488902
DOI: 10.1007/s00066-024-02202-0 -
Neuro-oncology Jul 2021
Topics: Humans; Meningeal Carcinomatosis; Meningeal Neoplasms; Prognosis
PubMed: 33830220
DOI: 10.1093/neuonc/noab051