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Ependymomas (EPN) are central nervous system neoplasms that exhibit an ependymal phenotype. In particular, supratentorial EPN (ST-EPN) must be differentiated from more aggressive entities such as glioblastoma, IDH-wildtype. This task is frequently addressed with the use of immunohistochemistry coupled with clinical presentation and morphological features. Here we describe the case of a young adult presenting with migraine-like symptoms and a temporoinsular-based expansile mass that was first diagnosed as a GBM, mostly based on strong and diffuse oligodendrocyte transcription factor 2 (OLIG2) expression. Molecular characterization revealed a ZFTA::RELA fusion, supporting the diagnosis of ST-EPN, ZFTA fusion-positive. OLIG2 expression is rarely reported in tumors other than GBM and oligodendrocyte-lineage committed neoplasms. The patient was treated with radiotherapy and temozolomide after surgery and was alive and well at follow-up. This report illustrates the need to assess immunostains within a broader clinical, morphological and molecular context to avoid premature exclusion of important differential diagnoses.

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Solitary fibrous tumor (SFT) is a rare fibroblastic mesenchymal neoplasm with an estimated annual incidence of 0.35 per 100,000 individuals. Doege-Potter syndrome is a paraneoplastic syndrome related to solitary fibrous tumor clinically characterized by hypoglycemia, occurring in less than 5% of cases. Herein, we report a case of metastatic SFT associated with recurrent severe hypoglycemia. A 43-year-old male with a noncontributory medical history presented with a painless and progressive growing mass in the right thigh. The histological evaluation rendered the diagnosis of SFT, and tumor resection was performed. One year after the operation, on the oncological follow-up, he was admitted to the emergency unit, manifesting an early-morning seizure associated with a severe hypoglycemia. The laboratory findings of non-islet cell tumor hypoglycemia (NICTH) in the background of a relapsed metastatic solitary fibrous tumor were consistent with the diagnosis of Doege-Potter syndrome. Hepatic embolization associated with oral glucocorticoid was an efficient palliative treatment to control the hypoglycemic crisis and allow hospital discharge.

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BACKGROUND: Cutaneous squamous-cell carcinoma (CSCC) is among the most frequent malignancies worldwide. For those not amenable to treatment with curative intent, immune checkpoint inhibition (ICI) with anti-programmed death receptor 1 (PD-1) antibodies has emerged as a novel therapeutic option. In this study, the authors sought to investigate the activity of the anti-PD-1 agent nivolumab in patients with advanced CSCC (aCSCC). METHODS: CA209-9JC was an open-label, single-arm, phase 2 study to evaluate the safety and/or efficacy of nivolumab in systemic treatment-naive patients with aCSCC. Nivolumab (3 mg/kg) was administered every 2 weeks until disease progression, unacceptable toxicity, or 12 months of treatment. The primary end point was the best objective response rate (BORR) as per RECIST 1.1 criteria. Secondary end points included safety, progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty-four patients with aCSCC were enrolled with a median age of 74 years (range, 48-93). Among the 24 patients evaluable for response, the BORR was 58.3% (14/24); there were no complete responses. With a median follow-up of 17.6 months, median duration of response has not been reached, and the estimated median PFS and OS were 12.7 and 20.7 months, respectively. Prior exposure to radiotherapy was associated with worse outcomes (p = .035, univariate analysis). Treatment-related adverse events of any grade and grade ≥ 3 occurred in 21 (87.5%) and six (25%) patients, respectively, and one patient discontinued nivolumab due to toxicities. CONCLUSIONS: Nivolumab resulted in robust antitumor activity, sustained responses, and good tolerability in systemic treatment-naive patients with aCSCC. These data provide further evidence to support the use of ICI as the standard treatment of aCSCC.

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ABSTRACT Solitary fibrous tumor (SFT) is a rare fibroblastic mesenchymal neoplasm with an estimated annual incidence of 0.35 per 100,000 individuals. Doege-Potter syndrome is a paraneoplastic syndrome related to solitary fibrous tumor clinically characterized by hypoglycemia, occurring in less than 5% of cases. Herein, we report a case of metastatic SFT associated with recurrent severe hypoglycemia. A 43-year-old male with a noncontributory medical history presented with a painless and progressive growing mass in the right thigh. The histological evaluation rendered the diagnosis of SFT, and tumor resection was performed. One year after the operation, on the oncological follow-up, he was admitted to the emergency unit, manifesting an early-morning seizure associated with a severe hypoglycemia. The laboratory findings of non-islet cell tumor hypoglycemia (NICTH) in the background of a relapsed metastatic solitary fibrous tumor were consistent with the diagnosis of Doege-Potter syndrome. Hepatic embolization associated with oral glucocorticoid was an efficient palliative treatment to control the hypoglycemic crisis and allow hospital discharge.

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Background: The majority of patients diagnosed with glioblastoma develop recurrent disease resulting in poor prognoses. The current study aimed to determine the survival rates of patients diagnosed with glioblastoma in Brazil accounting for the influence of age, treatment modalities, public and private practices, and educational level using a population-based national database. Methods: Patients diagnosed with glioblastoma from 1999-2020 were identified from The Fundação Oncocentro de São Paulo database to create a retrospective cohort. Patients were described according to age, education level treatment modalities and medical practice. In a Cox proportional hazards model, controlled for confounding factors for overall survival, the hazard ratio and 95% CI of overall survival in adults was evaluated. Findings: A total of 4,511 patients were included. The median lengths of survival for patients treated in the public and private settings were 8 and 17 months (p<0.001), respectively. Young patients had longer median overall survival (OS: 18 to 40 years, 41 to 60 years, 61 to 65 years, 66 to 70 years and over than 70 years was 22 months, 10 months, 6 months, 5 months, 4 months, respectively (p<0.001). In general, combined treatments were associated with higher median survival compared to monotherapy. The higher educational level, the higher median survival was observed (4 months for illiterate versus 14 months for university degree). In the multivariable analyses, the significant independent predictors for overall survival were practice setting, educational level, age and treatment modalities. Interpretation: Public practice, older patients, less intensive treatment, and lower educational level were associated with worse survival outcomes in Brazilian glioblastoma patients.

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PURPOSE: A substantial increase in melanoma incidence has been consistently observed worldwide over the past decades. However, melanoma mortality rates have remained stable or declined over the past years in most regions. Given the paucity of melanoma mortality data for different Brazilian regions, we sought to describe melanoma mortality trends in southeastern Brazil and their relationship with demographic variables. MATERIALS AND METHODS: A cross-sectional registry-based analysis was conducted to describe melanoma mortality trends in the state of São Paulo, Brazil, from 1996 to 2016. Demographic information from melanoma-related death records, including sex and age, was collected from the Fundação Sistema Estadual de Análise de Dados database. The annual percentage change (APC) was calculated to identify mortality trends over the period. RESULTS: An increasing melanoma mortality trend was detected among males, regardless of age (APC, 1.72%; P < .001), and was more pronounced for men ≥ 60 years old (APC, 2.63%; P < .001). Melanoma mortality rates have also increased for patients ≥ 60 years old, regardless of sex (APC, 1.11%; P < .001). A non-statistically significant increase in the overall melanoma mortality rate was observed over the 20-year period analyzed (APC, 0.36%; P = .4). CONCLUSION: Our data suggest a stable melanoma mortality over the past two decades for the overall population studied; however, a significant increase in melanoma mortality rates has been demonstrated among males and in the population ≥ 60 years old, emphasizing the need to implement prevention strategies and expand access to effective therapies for this population.

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Dermal sarcomas represent a group or rare malignancies of mesenchymal origin. Although surgical excision with wide margins can be curative, in the advanced/metastatic setting, treatment options are limited and the benefit from anthracycline-based chemotherapy or targeted agents is usually short-lived. Tumor mutational burden and PD-L1 expression scores can be used as predictive biomarker for response to immunotherapy in some metastatic cancers. The role of immune-checkpoint blockade for sarcoma patients remains investigational. Here we present three cases of dermal sarcomas with high TMB and PD-L1 expression and responses to anti-PD1 agents in two of them.

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BACKGROUND: NUT midline carcinoma is a rare and aggressive subset of squamous cell carcinoma, which is characterized by the translocation of nuclear protein in testis gene that is mostly fused with bromodomain and extraterminal family proteins. We describe here the first Brazilian case of NUT midline carcinoma with BRD4-NUT fusion detected in a next-generation sequencing panel and we present the clinical evolution of this patient. CASE PRESENTATION: A 42-year-old Caucasian man was diagnosed with poorly differentiated squamous cell carcinoma of the left maxillary sinus, with negative in situ hybridization for Epstein-Barr encoding region and human papillomavirus genotyping. He received induction therapy, chemoradiotherapy with weekly systemic chemotherapy, and, concurrently, weekly intra-arterial chemotherapy. New imaging evaluation, 1 month after the end of the last treatment, revealed a good partial response in the primary lesion. However, positron emission tomography-computed tomography showed multiple suspicious lesions in his bones and lungs, which were histologically confirmed. He died exactly 2 months after metastatic disease was diagnosed. CONCLUSIONS: NUT midline carcinoma is usually very aggressive. Currently, there is no standard of care for treatment of NUT midline carcinoma. The definitive diagnosis must be by demonstration of NUTM1 rearrangement. Immunohistochemical staining of greater than 50% of tumor nuclei on formalin-fixed paraffin-embedded tissue using the monoclonal rabbit antibody to NUT (clone C52B1), has a specificity of 100%, and sensitivity of 87% for the diagnosis of NUT midline carcinoma. Our case is the first Brazilian case of NUT midline carcinoma with BRD4-NUT fusion.

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INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant tumor from the central nervous system in adults. However, the presence of systemic metastasis is an extremely rare event. The objective of this study was to review the literature, evaluating the possible biological mechanisms related to the occurrence of systemic metastasis in patients diagnosed with GBM. RESULTS: The mechanisms that may be related to GBM systemic dissemination are the blood-brain barrier breach, often seen in GBM cases, by the tumor itself or by surgical procedures, gaining access to blood and lymphatic vessels, associated with the acquisition of mesenchymal features of invasiveness, resistance to the immune mechanisms of defense and hostile environment through quiescence. CONCLUSIONS: Tumor cells must overcome many obstacles until the development of systemic metastasis. The physiologic mechanisms are not completely clear. Although not fully understood, the pathophysiological understanding of the mechanisms that may be associated with the systemic spread is salutary for a global understanding of the disease. In addition, this knowledge may be used as a basis for a therapy to be performed in patients diagnosed with GBM distant metastasis.

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