A Cerebellar Tumor-to-Tumor Metastasis in a Patient With Von Hippel-Lindau Disease.

Tumor-to-tumor metastasis in the central nerve system is uncommon in our routine practice. Most reports include metastatic breast cancer into meningioma. Here we report a metastatic clear cell renal cell carcinoma (ccRCC) into a cerebellar hemangioblastoma in a patient with von Hippel-Lindau (VHL) disease. Imaging cannot distinguish metastatic ccRCC from primary cerebellar hemangioblastoma. Immuno-molecular studies are proven to be diagnostic. We also reviewed previously documented tumor-to-tumor metastasis of ccRCC to cerebellar hemangioblastoma in VHL disease. Lastly, we discussed potential mechanisms involved in the metastasis of ccRCC to hemangioblastoma in the cerebellum in patients with VHL.

A Rare Case of Pancreatoblastoma with Intracranial Seeding.

BACKGROUND: Pancreatoblastoma is an extremely rare neoplasm that accounts for 0.5% of all pancreatic exocrine tumors. These rare entities typically manifest in the pediatric population but can rarely occur in adults. Systemic seeding has been described before but intracranial metastasis in adults has yet to be described. CASE DESCRIPTION: A 28-year-old woman with a history of pancreatoblastoma that had been in remission for 51 months after treatment with cisplatin, doxorubicin (Adriamycin), and etoposide had presented to the emergency room with chronic recurrent headaches. Conservative management of the headaches failed, which led to a diagnostic workup with magnetic resonance imaging of the brain. Magnetic resonance imaging demonstrated a well-circumscribed solitary cerebellar lesion. Metastatic disease was suspected, and the patient underwent suboccipital craniotomy for tumor resection with adjuvant gamma knife radiosurgery. CONCLUSIONS: Central nervous system seeding of pancreatoblastoma is rare, and the available evidence suggests that the strategy we used could be adequate for treating such occurrences.

Worsening of anti-Hu paraneoplastic neurological syndrome related to anti-PD-1 treatment: Case report and review of literature.

We present an illustrative case of a 62-year-old woman with small cell lung cancer who developed progressive worsening of pre-existing anti-Hu antibody associated sensory neuronopathy after treatment with programmed cell death-1 (PD-1) inhibitor, nivolumab. We review the literature and identify 6 reported cases to understand the clinical outcomes of patients with anti-Hu paraneoplastic neurologic syndrome (PNS) treated with anti-PD-1 treatment. The PNS clinical spectrum comprised of encephalitis, a combination of sensory neuronopathy and anti-NMDAR encephalitis, isolated sensory neuronopathy, and encephalomyelitis. Immune checkpoint inhibitor have the potential to worsen pre-existing anti-Hu PNS and may promote the development of anti-Hu PNS.

Triple-Negative Lobular Breast Cancer Causing Hydronephrosis.

Breast cancer is the leading malignancy and the second most common cause of mortality in women. Although there have been advances in identifying biomarkers as potential targets for therapy, triple-negative breast cancer (TNBC) continues to have a poorer prognosis than the other receptor subtypes. The most common sites of metastasis are bone, liver, lung, and brain. We present a patient with known TNBC presenting with nausea and vomiting in whom computed tomography revealed a right-side pelvic mass causing hydronephrosis. Biopsy was consistent with TNBC of the ureter, an unusual site for breast cancer involvement. She required ureteral stent placement to relieve obstruction and has had good response to paclitaxel. Hydronephrosis due to malignancy presents significant risk of morbidity and mortality due to compromised renal function and must be resolved promptly to avoid compromise of renal function.

Cerebellar Metastasis From Ovarian Carcinoma Harboring PIK3CA-Activating Mutation: A "Clear" Explanation for Unexpected "Vertigo".

Brain metastasis is a rare and generally late manifestation of an advanced-stage, high-grade serous ovarian carcinoma. Nowadays, the improved control of intra-abdominal disease by surgery and platinum-based chemotherapy results in a longer survival, allowing distant metastasis to implant and grow in the brain parenchyma. Herein, we describe a unique case of a cerebellar metastasis from clear cell ovarian carcinoma that initially presented as a FIGO Stage IC cancer. Surprisingly, 6 mo after surgery, the patient was in good condition with complete disappearance of symptoms and no evidence of recurrence. This relatively good biologic behavior may be explained by the presence of a PIK3CA-activating mutation in exon 9 which as previously reported in the literature, may be associated with better prognosis. To the best of our knowledge, this is the first reported case of cerebellar metastasis from ovarian clear cell carcinoma. In the presence of neurological symptoms, both clinicians and pathologists must be aware of this rare possibility, to assure correct patient management and effective therapeutic options. Generally, the prognosis of epithelial ovarian cancer patients with brain metastases is poor. PIK3CA mutations could be a good prognostic indicator in clear cell carcinomas.

T2 Hypointensity Aids in the Diagnosis of Intracranial Metastatic Adenocarcinoma.

BACKGROUND: The T2 hypointensity has been suggested to be associated with intracranial metastatic adenocarcinomas (IMA). The purpose of our study was to determine the association of T2 hypointensity with IMA. METHODS: All patients with pathologically confirmed metastatic brain tumors who had a magnetic resonance imaging (MRI) at our institution in the last 10 years were retrospectively assessed. Qualitative assessment of the lesions on MRI was done by two separate readers who were blinded to the pathological diagnosis. For qualitative assessment, the T2 hypointensity in the lesion was compared with the contralateral normal appearing white matter. Odds ratio, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Of 107 patients with intracranial metastasis, only 73 (40 females; 33 males; mean age 61 years) had MRI available for review. Of these, only 46 (25 females; 21 males; mean age 61 years) had pathologically proven IMA. T2 hypointensity was seen in 20% of IMA. The odds ratio of T2 hypointensity in IMA was 3 compared to nonadenocarcinomas but was not statistically significant (p = 0.16). Intralesional hemorrhage was seen in 20. When controlled for hemorrhage, the odds ratio for T2 hypointensity in IMA was 4.7. The specificity, sensitivity, PPV, and NPV for T2 hypointensity to diagnose IMA were 92%, 19%, 81%, and 40%, respectively. CONCLUSION: T2 hypointensity was seen only in 20% of IMA with an odds ratio of 4.7. T2 hypointensity showed a high specificity and PPV for diagnosis of IMA.

Solitary Cerebellar Metastasis of Ovarian Cancer Detected by FDG PET/CT.

Ovarian cancer with solitary metastasis to the cerebellum is very rare. We presented a 58-year-old woman complaining of headaches 9 months after debulking surgery and chemotherapy due to ovarian cancer. The serum CA125 level was elevated. FDG PET/CT was then recommended to identify potential malignancy and showed a hypermetabolic mass in the right cerebellum. The cerebellar mass was surgically removed, and the pathology confirmed metastasis from ovarian cancer.

Clinical and Radiological Characteristics of Malignant Tumors Located to the Cerebellopontine Angle and/or Internal Acoustic Meatus.

OBJECTIVE: Metastatic lesions to the internal auditory meatus (IAM) and/or the cerebellopontine angle (CPA) are rare and may appear like a vestibular schwannoma (VS). We herein raise the issue of the diagnosis and treatment of nine malignant cases of the CPA and IAM among three referral centers in France and Japan. The aim of this study was 1) to report malignant lesions of the CPA, their diagnosis and treatment, 2) to review the literature, 3) to propose criteria of suspicion for malignant tumors of the CPA. METHODS: Nine patients who had malignant lesions of the CPA and/or IAM for whom the final diagnosis was made by surgery, lumbar puncture, or PET scan were included. The main outcomes measured were: rapid onset of symptoms, association of cochlea-vestibular symptoms with facial palsy, and MRI analysis. RESULTS: Among the nine patients with malignant tumor of the CPA, 8 of them (89%) had a facial palsy associated with cochlea-vestibular symptoms. Rapid growth of the tumor was observed in 77% (7/9) of the cases in a mean time interval of 4.6 months. The initial diagnosis evoked was VS in 44% of the cases (4/9). Atypical MRI aspect was seen in 67% of the cases (6/9) with bilateral tumors in 55% of cases (5/9). CONCLUSION: Although rare, malignant tumors of the CPA and/or IAM should be evoked in case of association of cochleovestibular symptoms and facial palsy, rapid onset and atypical MRI aspect.

Cerebellar Metastasis of Unknown Primary Neuroendocrine Carcinoma: Report of Case Mimicking Hemangioblastoma.

BACKGROUND: Neuroendocrine carcinoma (NEC) originates with neuroendocrine cells and is mainly found in the pancreas, lungs and gastrointestinal tract. We surgically treated a case of primary unknown NEC with only cerebral metastasis that mimicked hemangioblastoma. Recurrence was seen at the fornix, and no primary lesion had been identified as of 2 years after treatments despite careful examination. CASE DESCRIPTION: A 61-year-old man presented with dizziness. Past medical history included hypertension, dyslipidemia, hyperuricemia and colon polyp. We performed magnetic resonance imaging (MRI) to examine the cause of dizziness, revealing tumor with enhancement and peritumoral edema at the right cerebral lesion. Contrast-enhanced whole-body computed tomography (CT) showed no other lesions. We suspected hemangioblastoma from examinations and decided on surgical resection. Neuropathologically, the resected tumor was diagnosed as brain metastasis of NEC, but CT, fluorodeoxyglucose-positron emission tomography, gastrointestinal endoscopy, and somatostatin receptor scintigraphy all failed to reveal the primary lesion. As postoperative MRI showed enhancement around the resection cavity and at the right fornix, radiotherapy was performed. No other lesions were seen at 24 months postoperatively. We are continuing careful monitoring and no chemotherapy has been administered. CONCLUSIONS: We treated brain metastasis from NEC of unknown primary and mimicking hemangioblastoma using only local treatment. When an enhancing, single, solid tumor is seen in the cerebellum, brain metastasis from NEC of unknown primary is 1 differential diagnosis.

Re-expansion pulmonary edema after resection of cerebellar lesion in a patient with bronchial occupying lesion: A case report.

RATIONALE: Re-expansion pulmonary edema (RPE) is a non-cardiogenic pulmonary edema, and is secondary to pulmonary collapse caused due to various reasons. However, RPE is rarely encountered during non-thoracic surgeries and is associated with much higher risk than that occurring in thoracic surgeries. PATIENT CONCERNS: Herein we have reported a case report of a 55-years-old male patient. Preoperative examination indicated occupying lesions in the bronchus and cerebellar hemisphere. Under general anesthesia, the patient received resection of cerebellar lesion and developed acute atelectasis, and RPE occurred when cannulation was withdrawn after re-expansion. Supportive and symptomatic treatment was given to the patient for recovery well. DIAGNOSIS: RPE. INTERVENTIONS: The trachea was cannulated and connected to a ventilator for assisted ventilation. The patient was also given symptomatic treatment including nebulization, diuresis, and anti-inflammation. OUTCOMES: The patient recovered well and was discharged on day 8 after surgery. LESSONS: Patients with occupying lesions of the airway should undergo bronchoscopy to determine the location, size, and distance of the lesion from the incisors. The anesthesiologists should determine appropriate anesthetic regimens according to the examination results to avoid acute atelectasis and postoperative pulmonary edema.

Telomere elongation via alternative lengthening of telomeres (ALT) and telomerase activation in primary metastatic medulloblastoma of childhood.

PURPOSE: Elongation of telomeres is necessary for tumor cell immortalization and senescence escape; neoplastic cells use to alternative pathways to elongate telomeres: telomerase reactivation or a telomerase-independent mechanism termed alternative lengthening of telomeres (ALT). Telomerase and ALT pathway has been explored in adult and pediatric gliomas and medulloblastomas (MDBs); however, these mechanisms were not previously investigated in MDBs metastatic at the onset. Therefore, we analyzed the activation of telomerase and ALT pathway in a homogenous cohort of 43 pediatric metastatic medulloblastomas, to investigate whether telomere elongation could play a role in the biology of metastatic MDB. METHODS: We evaluated telomeres length via telomere-specific fluorescence in situ hybridization (Telo-FISH); we assessed nuclear expression of ATRX by immunohistochemistry (IHC). H3F3A and TERT promoter mutations were analyzed by pyrosequencing, while UTSS methylation status was analyzed via methylation-specific-PCR (MS-PCR). RESULTS: H3F3A mutations were absent in all MDBs, 30% of samples showed ATRX nuclear loss, 18.2% of cases were characterized by TERT promoter mutations, while 60.9% harboured TERT promoter hyper-methylation in the UTSS region. Elongation of telomeres was found in 42.8% of cases. Metastatic MDBs control telomere elongation via telomerase activation (10.7%), induced by TERT promoter mutations in association with UTSS hyper-methylation, and ALT mechanism (32.1%), triggered by ATRX inactivation. Among non-metastatic MDBs, only 5.9% (1/17) showed ATRX nuclear loss with activation of ALT. CONCLUSIONS: Our metastatic cases frequently activate ALT pathway, suggesting that it is a common process for senescence escape in primary metastatic medulloblastomas. Furthermore, the activation of mechanisms for telomere elongation is not restricted to certain molecular subgroups in this high-risk group of MDBs.

Hypothalamic hypopituitarism secondary to suprasellar metastases from small cell lung cancer: a case report and review of the literature.

BACKGROUND: Metastasis to the pituitary gland is an infrequent clinical problem, and the symptoms caused by metastases have been reported in only 2.5-18.2% of the cases. However, metastasis to the suprasellar lesion has rarely been reported in the literature. To the best of our knowledge, only nine cases of hypothalamic hypopituitarism due to metastases of solid tumors have been reported in English-language journals. CASE PRESENTATION: A 67-year-old Japanese man presented to our hospital with generalized weakness, lethargy, and weight loss. Laboratory data showed hypoglycemia together with low thyroid-stimulating hormone and free thyroxine. We suspected hypopituitarism and performed imaging of the head, which revealed multiple tumors, one of which was in the suprasellar region. Computed tomography of the chest showed a tumor shadow, and a bronchoscopic biopsy pathologically showed small cell lung cancer. Hormone profiling demonstrated hypothalamic pan-hypopituitarism. We diagnosed hypothalamic hypopituitarism secondary to metastases from the primary lung cancer and initiated radiation, chemotherapy, and hormone replacement, but the patient died 10 months later. CONCLUSIONS: We report a case of a 67-year-old man with hypothalamic hypopituitarism secondary to a suprasellar metastasis from a primary small cell lung cancer, and we review ten cases of hypothalamic hypopituitarism due to metastases, including our patient. Recognizing hypopituitarism can be challenging, especially in the elderly, whose symptoms such as lethargy and visual decline may be mistaken for the natural aging process. In patients with established metastatic conditions, the symptoms may be wrongly attributed to malignancy or to the side effects of therapy. When a patient is suspected of having hypopituitarism, a hormone load test can help to diagnose the type of hypopituitarism. It is important to evaluate the brain and the whole body to confirm whether metastasis and primary cancer exist. Because the mortality rate is very high, aggressive intervention for both diagnosis and therapy is required in cases of hypothalamic hypopituitarism secondary to tumor metastasis.

Metastatic pancreatic adenocarcinoma presenting as an occipital haemorrhage.

We report a case of a 63-year-old woman who was presented to the emergency department with an occipital haemorrhage secondary to a pancreatic cerebral metastasis. Pancreatic cancer is the ninth most common cancer in women in Australia, and distant disease is present in 70% of patients with pancreatic cancer at the time of diagnosis. However, metastases to the brain are rare, accounting for only 0.33%-0.57% cases antemortem. Herein, we discuss the management of this unusual case to highlight the importance of recognising unusual central nervous system involvement of cancers, a problem which may be increasing in prevalence.