Miliary Brain Metastases Research Articles

Central Nervous System Miliary Brain Metastasis Secondary to Breast Cancer.

Miliary metastasis to the central nervous system (CNS) is a rare presentation of metastasis mainly found in primary adenocarcinoma of the lung. Its association with breast cancer is even less frequent. We present the case of a 50-year-old female patient diagnosed in 2010 with stage IIA infiltrating ductal breast cancer RE (-), RP (+), HER 2 (-), HER2 NEU (+). She was treated with modified radical left breast mastectomy, radiation therapy, and chemotherapy. Her condition began presenting oppressive frontal headache without irradiation, predominantly in the evening, intensity 8/10, which decreased when sleeping and was exacerbated with stressful situations, in addition to progressive cognitive deterioration. Simple and contrasted computed tomography (CT) of the skull and thoracoabdominal were requested, showing multiple micronodular lesions with calcium density in the brain parenchyma, left pleural effusion, hypo and hyperdense lesions in the liver parenchyma, as well as osteoblastic lesions in the lumbar spine. Simple and contrasted magnetic resonance imaging (MRI) of the skull showed multiple supra and infratentorial intra-axial lesions. The most frequent associated symptom with miliary metastasis is cognitive impairment. Miliary metastasis, confirmed by imaging studies and histopathology, requires the ruling out of other causes of this calcification pattern, such as neurocysticercosis, due to specific treatment for each pathology.

Miliary Brain Metastasis-A Rare Pattern of Metastases from Breast Cancer.

Miliary Brain Metastasis-A Rare Pattern of Metastases from Breast Cancer.

Miliary brain metastases from primary breast carcinoma: a case report

Miliary brain metastases from primary breast carcinoma: a case report

Rare Presentation of Miliary Brain Metastasis in Absence of TypicallyAssociated Mutation

Lung cancer frequently presents with metastasis to the brain. Previously multiple metastases to the brain, described as miliary metastasis, have been reported with lung cancer and more commonly adenocarcinoma subtype. Various gene mutations involving exon 19, exon 20 and exon 21 have been reported with such metastasis. Though the prognosis is poor it is useful to identify such spread in order to tailor the treatment plan for a patient. We present a case of miliary metastasis to the brain in a patient with Grade IVa lung cancer presenting with confusion and speech difficulties.

Miliaire cérébrale carcinomateuse secondaire a un adénocarcinome pulmonaire muté EGFR

Miliary brain metastases are a rare form of brain metastatic lesions. We report the case of a 58-year-old patient with lung adenocarcinoma and an EGFR mutation, who had metastatic lesions in the bones, pleura and pericardia at the time of diagnosis. The patient was treated with tyrosine kinase inhibitor. A few months later, he presented with progressive neuropsychiatric symptoms, which were attributed to miliary brain metastases based on the radiological pattern (micronodules, some of which were calcified) and the elimination of alternative possible diagnoses. Despite tumour stability in the thorax and metastatic sites other than the brain, his neurological condition deteriorated, even after cerebral radiotherapy, leading to his death eight months after the diagnosis of lung cancer. Miliary brain metastases are a rare form of brain metastases with unusual clinical presentation. The diagnosis is based on the radiological pattern of cerebral miliary dissemination, with sometimes calcified tumor nodules. Despite its rarity, several cases have been reported in lung adenocarcinoma in the presence of EGFR mutations.

Miliary brain metastases from papillary adenocarcinoma of the lung – unusual MRI pattern with histopathologic correlation

SummaryMiliary brain metastases are very rarely described in the literature but if they are, they are quite obvious on magnetic resonance imaging (MRI) and enhance after intravenous administration of the contrast medium. The authors presented a case of miliary metastatic spread to the brain which was invisible on computed tomography and hardly visible on MRI, i.e. as countless, tiny, slightly T1-hyperintense foci that did not enhance. The authors discussed a few T1-hyperintense brain lesions which did not include metastases (except for metastatic melanoma which was a radiological suggestion after brain MRI). Autopsy revealed papillary adenocarcinoma of the lung with numerous metastatic lesions in both cerebral and cerebellar hemispheres and the meninges.

Introduction - Supplement on brain metastases

As therapeutic interventions for systemic solid neoplasms continue to improve, so do median survival times and the incidence of “safe harbor” metastases. Improvements in oncologic armamentaria for the cancers that have a predilection to metastasize to the central nervous system – breast, lung, melanoma, and renal cancers – have subsequently increased the likelihood of developing brain metastases. As neurosurgeons, we are involved in delivering two of the three most common therapies for brain metastases, surgery and stereotactic radiosurgery. With the discovery of metastatic disease in the brain, a patient, by definition, has stage IV cancer. However, unlike glioblastoma, there is a significant tail to the survival curve for stage IV cancer. Although glioblastoma carries a better median survival than brain metastases (12-13 months versus 8-10 months, respectively), glioblastoma carries a much lower 5-year survival rate (less than 5% versus almost 20%). While this is important to consider when choosing among treatment options, it also leads to a difficult clinical conundrum: Should we choose treatments based on the majority of patients, or do we treat patients as though they will be long-term survivors? While this may seem prima facie obvious, every treatment carries risks as well as benefits. Complicating this issue is the fact that current standard therapies have relatively equivalent impacts (as measured by local recurrence at one year and by median survival). Furthermore, as long as brain metastases are treated, the vast majority of patients will succumb to progression of systemic disease, not to their brain metastases. Brain metastases are a harbinger of systemic disease progression. Choosing brain metastasis therapy can be straightforward. A large, solitary, posterior fossa metastasis, with secondary hydrocephalus, in a young healthy patient with controlled systemic disease and a good performance status should undergo surgical resection. A patient with miliary brain metastases, too numerous to count, is best served by whole brain radiotherapy. A patient with three asymptomatic, inoperable metastases might best be treated with stereotactic radiosurgery. Unfortunately, these clear-cut cases are the exception. Proponents of each of these treatments must temper their enthusiasm and accept the need for a multi-faceted therapeutic approach, taking into account each patient's unique way of balancing length of survival and quality of life. The overarching goal of this Surgical Neurology International Supplement is to provide the neurosurgical community with an eclectic perspective. While we must rely on our medical oncology and radiation oncology colleagues to provide systemic treatments, in order to optimize patient care for brain metastases, neurosurgeons must participate in multidisciplinary teams that make decisions driven by consensus. Multidisciplinary teams offer an improved knowledge base and a greater likelihood of evidence-based decision-making. Hopefully, this collection of reviews will provide the reader with an improved understanding of the current state of knowledge of brain metastases development, epidemiology, pathology, treatment options, controversies, and future directions.

Miliary brain metastasis presenting with calcification in a patient with lung cancer: a case report

IntroductionMiliary brain metastasis is an extremely rare form of brain metastasis which can present with atypical imaging findings. We report the case of a patient with miliary brain metastasis of lung cancer showing calcification in metastatic lesions.Case presentationA 68-year-old Japanese woman was diagnosed with lung adenocarcinoma. Brain computed tomography revealed multiple small calcified lesions in both cerebral hemispheres. Mutation of the epidermal growth factor receptor gene (exon 21, L858R) in lung cancer cells was detected, and treatment with gefitinib was initiated. A partial response was observed; however, the patient was readmitted to our hospital because of regrowth of the primary lesion and complaints of nausea, headache, and difficulty walking. Brain magnetic resonance imaging revealed scattered tiny nodules enhanced by gadolinium. A diagnosis of leptomeningeal carcinomatosis was made on the basis of cerebrospinal fluid cytology. The patient’s general status worsened, and she died 356 days after the day of first medical examination. Upon autopsy, the brain was found to be edematous and swollen. Lung carcinoma cells were diffusely disseminated on the meningeal surface. Metastatic foci of small nodular form, accompanied by calcifications, were also found in the brain parenchyma. We diagnosed miliary metastasis of lung carcinoma.ConclusionsTo the best of our knowledge, this is the third report of calcified miliary brain metastasis confirmed by autopsy. We describe calcified lesions that increased in size during the clinical course of nine months. Brain computed tomography findings that reveal multiple small calcified lesions in patients with malignancy should raise suspicion of miliary brain metastasis.

Miliary brain metastases from occult lung adenocarcinoma: Radiologic and histopathologic confirmation

“Miliary brain metastases”, also termed as “Carcinomatous encephalitis”, are an extremely rare form of cerebral metastasis. Here in this article, we report a 52 year-old male patient with miliary brain metastases originating from occult lung adenocarcinoma. There were no significant findings on his initial physical and neurological examinations except limited cooperation. Brain computed tomography revealed edematous regions at the inferior sections of both parietal lobes. Then after, the contrast-enhanced magnetic resonance imaging revealed innumerable multi-dimensional lesions associated with surrounding edema on T2-weighted images. The proton magnetic resonance spectroscopy revealed increases in the choline and lipid peaks with decreased N-acetylaspartate in a similar manner with metastatic brain tumors. Histopathological findings pointed out that malignant epithelial tumor metastasis were originating in primary lung adenocarcinoma. Despite the advances in technical equipments and medical knowledge, miliary metastatic brain tumors are quite rare and the differential diagnosis is difficult. Our aim in this article was to present this rare case in which the lung was thought to be the primary focus; and outline the radiological characteristics. Also, we believe that the findings presented by proton magnetic resonance spectroscopy may contribute to making a differential diagnosis.

Miliary brain metastases in 2 cases with advanced non-small cell lung cancer harboring EGFR mutation during gefitinib treatment

Here we report 2 cases of non-small cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor (EGFR) gene mutation that developed miliary brain metastases characterized by dementia and disorientation during gefitinib therapy. One patient's therapy was switched from gefitinib to chemotherapy followed by whole brain radiotherapy (WBRT), which resulted in disease progression with coma. Gefitinib reinitiation improved the patient's symptoms. The other patient continued gefitinib during WBRT and achieved complete remission of the miliary metastases and lived 18 months longer. These results suggest that gefitinib concomitant with WBRT is an optional strategy for the treatment of patients with EGFR-mutated NSCLC with miliary metastases to prevent disease flare.

Metastatic brain tumors from non-small cell lung cancer with EGFR mutations: Distinguishing influence of exon 19 deletion on radiographic features

IntroductionMiliary brain metastasis is a rarity and refers to the presence of numerous small tumors in a perivascular distribution without intraparenchymal invasion and focal edema. Although the presence of epidermal growth factor receptor (EGFR) mutation and good response to gefitinib have been reported in non-small cell lung cancer (NSCLC) patients with miliary brain metastases, the influence of the EGFR mutations on the radiographic features remains unclear. Patients and methodsAll NSCLC patients with synchronous brain metastases detected at the time of a new diagnosis of NSCLC from March 2005 through May 2011 were divided according to EGFR mutation status. The number of brain tumors, size of the largest brain tumors, and size of peritumoral brain edema were compared among the groups. ResultsFifty-seven patients who met the criteria were divided into three groups: wild-type EGFR group (31 patients), exon 19 deletion group (18 patients), and exon 21 point mutation group (8 patients). The exon 19 deletion group had more multiple and smaller brain tumors with smaller peritumoral brain edema than did the wild-type group (P=0.024, P=0.0016, and P=0.0036, respectively). The exon 21 point mutation group showed no significant difference in any of the radiographic values when compared with the wild-type group. ConclusionOur results indicate that NSCLC patients with the exon 19 deletion have such a peculiar pattern of brain metastases as multiple small metastases with small brain edema. This metastatic pattern may be similar to that of miliary brain metastases. Because it is unclear whether or not severe neurologic symptoms develop during their clinical courses like miliary brain metastases, regular evaluation with brain magnetic resonance imaging (MRI) should be considered, regardless of the presence of neurologic symptoms. Accumulation of knowledge about specific pattern of brain metastasis will help approach to “individual” management.

A Case of Miliary Brain Metastasis of Lung Cancer Mimicking Neurocysticercosis

Miliary brain metastasis from the lung is uncommon and has a poor therapeutic response. We report a case of pulmonary adenocarcinoma combined with multiple brain cystic lesions that were initially misdiagnosed as neurocysticercosis. A 53-year-old male who never smoked was admitted to our hospital with complaints of agitation and cognitive impairment. Brain magnetic resonance imaging showed innumerable, small nodular lesions with a central, low signal intensity in whole brain parenchyma. His symptoms were not improved by the empirical praziquantel medication for disseminated neurocysticercosis. After a transbronchial biopsy from the right middle lobe, we could diagnose the primary lung adenocarcinoma with a single nucleotide polymorphism in the epidermal growth factor receptor exon 20 at codon 787 (Q787Q). His neurologic symptoms and imaging findings have been gradually improving with a first-line Gefitinib treatment for five months. We recommend a more active diagnostic approach including biopsy in case of atypical imaging findings.

Miliary Brain Metastases in Lung Cancer

Miliary Brain Metastases in Lung Cancer

Miliary brain metastasis presenting with dementia: Progression pattern of cancer metastases in the cerebral cortex

We report an autopsy case of an 82-year-old woman with progressive dementia due to miliary brain metastasis from lung adenocarcinoma. The patient presented with dementia 5 months prior to death and suddenly died of pulmonary hemorrhage. Postmortem examination revealed normal appearance of the brain. However, there were numerous foci of cancer metastasis in all parts of the brain on light microscopic examination. The carcinoma cells were located in the perivascular (Virchow-Robin) space and did not invade to the brain parenchyma. The carcinoma cells were also found in the subpial space. In the cerebral cortex, foci of metastasis appeared to spread in the following way: tiny foci of metastasis initially occur in the middle cortical layer, then spread to all layers through the perivascular space, and finally reach the subpial space and subcortical white matter. Although the junction between gray and white matter is a preferred site for usual brain metastasis, middle cortical layer was considered to be the initial site for metastasis in our patient. The perivascular pial sheath plays an important role for the development of miliary brain metastasis.

Miliary brain metastases from adenocarcinoma of the lung: MR imaging findings with clinical and post-mortem histopathologic correlation

Miliary brain metastases from adenocarcinoma of the lung: MR imaging findings with clinical and post-mortem histopathologic correlation

Miliary brain metastases from adenocarcinoma of the lung: MR imaging findings with clinical and post-mortem histopathologic correlation

Miliary dissemination is a rare form of brain metastasis. The clinical and pathologic features of this form are unclear. We report a 66-year-old man with miliary brain metastases from adenocarcinoma of the lung, describing MRI and neuropathologic findings in the context of previously reported cases. Initial disorientation progressed to an apallic state within 6 months. Although, CT with administration of contrast agent failed to demonstrate any lesions, MRI with Gd-DTPA administration showed multiple enhancing miliary nodules in the cerebral cortex, basal ganglia, thalamus, cerebellum, and brainstem. Some of those nodules also could be seen on T2-weighted imaging without Gd-DTPA, but were difficult to identify conclusively. A histopathologic examination at autopsy disclosed diffusely distributed miliary tumor nodules in a perivascular distribution without surrounding focal edema or reactive gliosis. Notably, this patient with miliary brain metastases developed disorientation followed by unconsciousness, which overshadowed other focal neurologic signs at that time. We should consider this pattern of brain dissemination when a cancer is associated with unexplained disturbance of consciousness.

Miliary brain metastases from primary gastric small cell carcinoma: illustrating the seed and soil hypothesis

Miliary brain metastases from primary gastric small cell carcinoma: illustrating the seed and soil hypothesis

Miliary brain metastases presenting as rapidly progressive dementia

We report the case of a 79-year-old woman who developed a rapidly progressive dementia (RPD) with severe memory impairment, early visual hallucinations and extrapyramidal signs. Symptoms started suddenly after hip replacement surgery following an accidental fall. Motor epileptic seizures appeared at the end of the illness. Dementia worsened gradually leading to akinetic mutism. She died five and a half months after the onset of symptoms. MRI showed cerebral atrophy but failed to detect any other lesion. Results of all laboratory tests performed were negative. After the most frequent treatable diseases were excluded, the diagnosis of dementia with Lewy bodies was initially considered. CJD was also suggested based on the rapid evolution of the disease and the positivity of 14-3-3 protein in CSF. Neuropathological examination revealed an extensive miliary metastatic dissemination from an unknown primary adenocarcinoma. Pulmonary origin was suggested according to the immunohistochemical profile. Histopathological changes of Alzheimer's disease were also observed in the cerebral cortex and hippocampus. Neither Lewy bodies nor PrP deposits were found. The sudden onset of the dementia just after the hip replacement surgery raises the possibility of a pathological fracture with secondary tumoral microembolic dissemination. Despite its rarity, this entity should be included in the differential diagnosis of RPD. This case illustrates the definite importance of neuropathological post-mortem examination in order to elucidate the different types of dementia.