Longest survival with primary intracranial malignant melanoma: A case report and literature review.

BACKGROUND: Primary intracranial malignant melanoma (PIMM) is rare, and its prognosis is very poor. It is not clear what systematic treatment strategy can achieve long-term survival. This case study attempted to identify the optimal strategy for long-term survival outcomes by reviewing the PIMM patient with the longest survival following comprehensive treatment and by reviewing the related literature. CASE SUMMARY: The patient is a 47-year-old Chinese man who suffered from dizziness and gait disturbance. He underwent surgery for right cerebellum melanoma and was subsequently diagnosed by pathology in June 2000. After the surgery, the patient received three cycles of chemotherapy but relapsed locally within 4 mo. Following the second surgery for total tumor resection, the patient received an injection of Newcastle disease virus-modified tumor vaccine, interferon, and ß-elemene treatment. The patient was tumor-free with a normal life for 21 years before the onset of the recurrence of melanoma without any symptoms in July 2021. A third gross-total resection with adjuvant radiotherapy and temozolomide therapy was performed. Brain magnetic resonance imaging showed no residual tumor or recurrence 3 mo after the 3rd operation, and the patient recovered well without neurological dysfunction until the last follow-up in June 2022, which was 22 years following the initial treatment. CONCLUSION: It is important for patients with PIMM to receive comprehensive treatment to enable the application of the most appropriate treatment strategies. Long-term survival is not impossible in patients with these malignancies.

Driver mutations in ADGRL3 are involved in the evolution of ependymoma.

Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

Safety evaluation of high-dose BCNU-loaded biodegradable implants in Chinese patients with recurrent malignant gliomas.

OBJECTIVES: Malignant gliomas are common primary brain tumors with dismal prognosis. The blood-brain barrier and unacceptable systemic toxicity limit the employment of chemotherapeutic agents. BCNU-impregnated biodegradable polymers (Gliadel®) have been demonstrated to prolong the survival of patients with malignant gliomas. Until now, no biodegradable drug delivery system has been commercially available in China. In the present study, we evaluated the safety of implants with high-dose BCNU in Chinese patients with recurrent malignant gliomas. PATIENTS AND METHODS: Adults with supratentorial recurrent malignant glioma were eligible. High-dose BCNU-loaded PLGA implants (20mg of BCNU in each implant) were placed in the debulking cavity. The implants were investigated by a classical 3+3 design. Four levels of BCNU, up to 12 implants, were evaluated. Pharmacokinetic sampling was performed. The toxicity of the implants and the survival of patients were recorded. RESULTS: Fifteen recurrent patients were enrolled with 12 glioblastomas and 3 anaplastic gliomas. Among 15 patients, 3 were treated with 3 implants (60 mg of BCNU), 3 with 6 implants (120 mg), 3 with 9 implants (180 mg) and 6 with 12 implants (240 mg). No dose-limiting toxicity was observed in the cohort of patients. Subgaleal effusion was the most common adverse event, presenting in 7 patients (46.7%). The median overall survival (OS) was 322 days (95% CI, 173-471 days). The 6-month, 1-year and 2-year survival rates were 66.7%, 40% and 13.3%, respectively. CONCLUSIONS: The high-dose BCNU-loaded PLGA implants were safe for Chinese patients with recurrent malignant gliomas and further investigation for efficacy is warranted.

Neurosurgical interventions for patients with nasopharyngeal carcinoma: a single institution experience.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a frequent head and neck cancer in southern China and Southeast Asia. The majority of NPC patients are managed by radiation oncologists, medical oncologists and head and neck surgeons. Actually, neurosurgical interventions are warranted under specific circumstances. In this article, we described our experience as neurosurgeons in the management of NPC patients. METHODS: Medical records of NPC patients who received neurosurgical procedure at Sun Yat-sen University Cancer Center were reviewed. RESULTS: Twenty-seven patients were identified. Among 27 cases, neurosurgical procedures were performed in 18 (66.7%) with radiation-induced temporal necrosis, 2 (7.4%) with radiation-induced sarcoma, 4 (14.8%) with synchronous NPC with primary brain tumors, 2 (7.4%) with recurrent NPC involving skull base, and 1 (3.7%) with metachronous skull eosinophilic granuloma, respectively. The diagnosis is challenging in specific cases and initial misdiagnoses were found in 6 (22.2%) patients. CONCLUSIONS: For NPC patients with intracranial or skull lesions, the initial diagnosis can be occasionally difficult because of the presence or a history of NPC and related treatment. Unawareness of these entities can result in misdiagnosis and subsequent improper treatment. Neurosurgical interventions are necessary for the diagnosis and treatment for these patients.

Low expression of Beclin 1 and elevated expression of HIF-1α refine distant metastasis risk and predict poor prognosis of ER-positive, HER2-negative breast cancer.

Even though ER-positive, HER2-negative breast tumors represent a subset of breast cancers with a better clinical outcome, approximately 12.7 % of patients in this subgroup ultimately develop cancer-related mortality. Recent studies had confirmed that hypoxia-induced autophagy-related gene Beclin 1 expression might be important for disease progression and be correlated with patient outcome in several tumors. Here, we examined the autophagic Beclin 1 and hypoxic HIF-1α levels in 378 ER-positive, HER2-negative breast cancer patients by immunohistochemistry using tissue microarray. We found that Beclin 1 was highly expressed in normal mammary gland epithelia. In contrast, it was either not expressed or only moderately expressed in 78.0 % of breast adenocarcinoma tissue. Compared to the subset overexpressing Beclin 1, the subset in which Beclin 1 levels were reduced had a poor 5-year overall survival rate (OS, 85.1 % vs. 94.1 %, P = 0.005) and a poor distant metastasis-free survival (DMFS, 79.1 % vs. 89.3 %, P = 0.037). Cox multivariate analysis confirmed that Beclin 1 was indeed an independent prognostic factor for OS and DMFS. Additionally, Beclin 1 positively correlated with HIF-1α expression (r = 0.206, P < 0.001). Importantly, among patients with HIF-1α overexpression, low levels of Beclin 1 predicted a worse OS. Our study confirmed that deficiency of Beclin 1 was a negative prognostic factor for OS and DMFS in ER-positive, HER2-negative breast cancer. The combination of Beclin 1 and HIF-1α refined the risk definition of the patient subset and provided a novel way to identify those with a high risk of relapse.

Primary nasopharyngeal non-Hodgkin's lymphoma: imaging patterns on MR imaging.

OBJECTIVES: To summarize the distinct imaging features of different subtypes of primary nasopharyngeal non-Hodgkin's lymphomas (NHLs). MATERIALS AND METHODS: Clinical data and magnetic resonance imaging findings of 71 patients with histologically proven primary nasopharyngeal NHLs were retrospectively reviewed. The tumor distribution, signal intensity, lesion texture, contrast enhancement properties, extra-chamber involvement, regional structure invasion, and cervical lymphadenopathy were evaluated and compared between different subtypes of NHLs. RESULTS: Of the patients, 70.4% had B-cell lymphomas; 64.8% had symmetrical and diffuse involvement of nasopharynx walls; and 19.7% had superficial ulcerations. Extra-chamber involvement and regional structure invasion occurred in most patients. The frequency of neck node involvement was up to 83.10%; 62.7% of them were bilateral involvement. Patients with T-cell or nature killer/T-cell NHLs had a higher incidence of superficial ulcerations, nasal cavity, and paranasal sinus invasion than B-cell NHLs (P<.05). Patients with B-cell NHLs had a higher incidence of cervical lymphadenopathy specifically in Level VA and parotid region than T-cell or nature killer/T-cell (NK/T-cell) NHLs (P<.05). CONCLUSION: Primary nasopharyngeal NHLs had some characteristic imaging features and different subtypes of nasopharyngeal NHLs had some distinct imaging features.

Aurora-A activation, correlated with hypoxia-inducible factor-1α, promotes radiochemoresistance and predicts poor outcome for nasopharyngeal carcinoma.

Previously, we and others showed that hypoxia-inducible factor-1α (HIF-1α) and transcriptionally upregulated Aurora-A were required for disease progression in several tumors. Here, we address the clinicopathologic value of Aurora-A and HIF-1α in locally advanced nasopharyngeal carcinoma (NPC). Aurora-A and HIF-1α expression was semiquantitatively evaluated by immunohistochemistry staining in 144 cases from a randomized controlled trial. Of these patients, 69 received neoadjuvant chemotherapy plus concurrent chemoradiotherapy, and acted as the training set, and 75 cases treated with neoadjuvant chemotherapy plus radiotherapy were used as the testing set to validate the prognostic effect of Aurora-A and HIF-1α. We found that Aurora-A and HIF-1α were highly expressed in NPC, but were deficient in normal adjacent epithelia. In the testing set, Aurora-A overexpression predicted a shortened 5-year overall survival (59.1% vs 82.5%, P = 0.024), progression-free survival (44.8% vs 79.8%, P = 0.004), and distant metastasis-free survival (43.0% vs 17.3%, P = 0.016). Multivariate regression analysis confirmed that Aurora-A was indeed an independent prognostic factor for death, recurrence, and distant metastasis both in the testing set and overall patients. Moreover, a positive correlation between Aurora-A and HIF-1α was detected (P = 0.037). Importantly, although HIF-1α did not show any prognostic effect for patient outcome, the subset with Aurora-A and HIF-1α co-overexpression had the poorest overall, progression-free, and distant metastasis-free survival (all P < 0.05). Our results confirmed that Aurora-A was an independent prognostic factor for NPC. Aurora-A combined with HIF-1α refined the risk definition of the patient subset, thus potentially directing locally advanced NPC patients for more selective therapy.

Magnetic resonance imaging features of nasopharyngeal carcinoma and nasopharyngeal non-Hodgkin's lymphoma: are there differences?

PURPOSE: To describe differences in the primary tumour and distribution of cervical lymphadenopathy for cases of nasopharyngeal carcinoma (NPC) and nasopharyngeal non-Hodgkin's lymphoma (NPNHL) using magnetic resonance (MR) imaging. MATERIALS AND METHODS: MR images of patients with NPC (n = 272) and NPNHL (n = 118) were independently reviewed by two experienced radiologists. RESULTS: NPC had a higher incidence of tumour invasion associated with the levator and tensor muscles of the velum palatine, the longus colli and medial pterygoid muscles, the base of the pterygoid process, the clivus, the base and greater wing of the sphenoid bone, the petrous apex, the foramen lacerum, the foramen ovale, the hypoglossal canal, and intracranial infiltration. In contrast, NPNHL had a higher incidence of tumour invasion associated with the hypopharynx, the palatine and lingual tonsils, as well as the ethmoid and maxillary sinuses. NPNHL also had a higher incidence of extensive and irregular bilateral lymphadenopathy, and lymphadenopathy in the parotid. CONCLUSIONS: NPC more often involved an unsymmetrical tumour with a propensity to invade both widely and deeply into muscle tissue, the fat space, the neural foramen, and the skull base bone. In contrast, NPNHL tended to be a symmetrical and diffuse tumour with a propensity to spread laterally through the fat space and along the mucosa to the tonsils of the oropharynx and hypopharynx. These differences facilitate a differentiation of these diseases using MR images, and enhance our understanding of the biological behavior of these malignant tumours of the nasopharynx.

Nasopharyngeal adenoid cystic carcinoma: magnetic resonance imaging features in ten cases.

Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with high local invasiveness. To date, there is no consensus on the imaging characteristics of NACC. To address this, we retrospectively reviewed 10 cases of NACC and summarized the magnetic resonance imaging (MRI) features. MR images of 10 patients with histologically validated NACC were reviewed by two experienced radiologists. The location, shape, margin, signal intensity, lesion texture, contrast enhancement patterns, local invasion, and cervical lymphadenopathy of all tumors were evaluated. Clinical and pathologic records were also reviewed. No patients were positive for antibodies against Epstein-Barr virus (EBV). The imaging patterns of primary tumors were classified into two types as determined by location, shape, and margin. Of all patients, 7 had tumors with a type 1 imaging pattern and 3 had tumors with a type 2 imaging pattern. The 4 tubular NACCs were all homogeneous tumors, whereas 3 (60%) of 5 cribriform NACCs and the sole solid NACC were heterogeneous tumors with separations or central necrosis on MR images. Five patients had perineural infiltration and intracranial involvement, and only 2 had cervical lymphadenopathy. Based on these results, we conclude that NACC is a local, aggressive neoplasm that is often negative for EBV infection and associated with a low incidence of cervical lymphadenopathy. Furthermore, MRI features of NACC vary in locations and histological subtypes.

Computed tomographic findings of skull base bony changes after radiotherapy for nasopharyngeal carcinoma: implications for local recurrence.

OBJECTIVE: To evaluate bony changes in the skull base after radiotherapy by computed tomography (CT) and their correlation with local recurrence in patients with nasopharyngeal carcinoma (NPC) without previous involvement of the skull base. DESIGN: Retrospective study. SETTING: Sun-Yat Sen University Cancer Center. METHODS: The records of 80 patients with NPC during the period from January 1992 to December 2005 were reviewed. All patients had been treated with radical radiotherapy or chemoradiotherapy at standard doses and were followed up with plain and contrast-enhanced CT every 6 months for 45.5 (range 12-108) months. MAIN OUTCOME MEASURES: The types, areas, time of the first occurrence after radiotherapy and development of the postradiation bony changes of the skull base, and local recurrence rates of NPC were measured. RESULTS: Eighteen patients (22.5%) had sclerosis in some area of the skull base, and the sclerosis in 5 (27.8%) of these patients changed into osteoporosis in 1 to 5 years after its appearance. Seventeen patients (21.3%) had osteolysis. The local recurrence rate of patients with osteolysis was observed to be significantly higher than that of patients with sclerosis (p < .0001). CONCLUSIONS: The appearance of osteolytic changes in the skull base during follow-up of patients with NPC who had normal skull base morphology before treatment was associated with tumour recurrence.

Influence of blanching and grinding process with hot water on beany and non-beany flavor in soymilk.

A total of 8 beany odor-active compounds and 4 non-beany aroma-active compounds of traditional soymilk were identified through dynamic headspace dilution analysis (DHDA) and gas chromatography-olfactometry-mass spectrometry (GC-O-MS). To eliminate the beany flavors, soymilk was processed with hot water blanching and grinding for 2, 4, 6, 8, and 10 min with a temperature between 80 and 100 °C. A total of 5 beany odor-active compounds and 3 non-beany aroma-active compounds of this soymilk were analyzed by headspace solid phase microextraction (HS-SPME). As a result, lipoxygenase (LOX) activity gradually decreased by hot water treatment with time, and with the decrease of Lox activity, the 5 beany odor-active compounds and 3 non-beany aroma-active compounds were significantly decreased. However, the reduction in non-beany flavor compounds was smaller than for beany odor compounds. Therefore, a balance between beany and non-beany flavors can be reached in soymilk. When the soaked soybeans were blanched and ground with hot water for 2 to 6 min, the LOX activity was between 38% and 57% of the beginning activity. For these processing times, the non-beany compounds could be largely maintained. The ratio of the total peak area of the 3 non-beany aroma compounds and 5 beany flavor compounds was between 0.07 and 0.12, and the sensory scores of the aromas were higher than that of the off-flavors. Practical Application: Beany flavors in soymilk could be reduced with hot water blanching and grinding at temperature above 80 °C. However, the treatment of hot water blanching affected the non-beany aromas of soymilk. A suitable blanching and grinding time is necessary to achieve a balance of soymilk flavors.