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To elucidate the long‐term outcomes of non‐anthracycline‐containing therapies and central nervous system (CNS) events in patients with extranodal NK/T‐cell lymphoma, nasal type (ENKTL), the clinical data of 313 patients with ENKTL diagnosed between 2000 and 2013 in a nationwide retrospective study in Japan were updated and analyzed. At a median follow‐up of 8.4 years, the 5‐year overall survival (OS) and progression‐free survival (PFS) were 71% and 64%, respectively, in 140 localized ENKTL patients who received radiotherapy‐dexamethasone, etoposide, ifosfamide, and carboplatin (RT‐DeVIC) in clinical practice. Nine (6.4%) patients experienced second malignancies. In 155 localized ENKTL patients treated with RT‐DeVIC, 10 (6.5%) experienced CNS relapse (median, 12.8 months after diagnosis). In five of them, the events were confined to the CNS. Nine of the 10 patients who experienced CNS relapse died within 1 year after CNS relapse. Multivariate analysis identified gingival (hazard ratio [HR], 54.35; 95% confidence interval [CI], 8.60–343.35) and paranasal involvement (HR, 7.42; 95% CI, 1.78–30.89) as independent risk factors for CNS relapse. In 80 advanced ENKTL patients, 18 received steroid (dexamethasone), methotrexate, ifosfamide, L‐asparaginase, and etoposide (SMILE) chemotherapy as first‐line treatment. Patients who received SMILE as their first‐line treatment tended to have better OS than those who did not (p = 0.071). Six (7.5%) advanced ENKTL patients experienced isolated CNS relapse (median, 2.6 months after diagnosis) and died within 4 months of relapse. No second malignancies were documented in advanced ENKTL patients. In the entire cohort, the median OS after first relapse or progression was 4.6 months. 12 patients who survived 5 years after PFS events were disease‐free at the last follow‐up. Of those, 11 (92%) underwent hematopoietic stem cell transplantation. Our 8‐year follow‐up revealed the long‐term efficacy and safety of RT‐DeVIC and SMILE. The risk of CNS relapse is an important consideration in advanced ENKTL. [ABSTRACT FROM AUTHOR]

We describe a case of an anaplastic lymphoma kinase (ALK)‐rearranged non‐small cell lung cancer with development of uterine metastasis after crizotinib and alectinib treatment. Gene analysis from the tissue of uterine metastasis revealed the presence of 1151Tins, which was considered to be a crizotinib and alectinib resistance mutation. Subsequent therapy with the third‐generation ALK inhibitor lorlatinib, but not ceritinib, showed antitumor activity for 1 year. The uterus is an uncommon site for metastasis from lung cancer, and our case indicated that serial gene analysis could provide new information about ALK inhibitor resistance. [ABSTRACT FROM AUTHOR]

Background: This study was performed to clarify the treatment outcome of patients with primary mediastinal germ cell tumors (PMGCTs), focusing on the clinical manifestations and management during definitive therapy and long‐term follow‐up. Methods: In this study, we retrospectively reviewed the medical records of patients with PMGCTs treated at Shinshu University School of Medicine, and examined the clinical profiles and treatment outcomes of 22 patients (mean age of 29 years) with primary mediastinal GCTs treated at our hospital between 1983 and 2019. Results: Five patients were diagnosed with pure seminoma and 17 had nonseminomatous GCT. A total of 21 patients were treated with cisplatin‐based chemotherapy and 15 patients (68.2%) underwent thoracic surgery after chemotherapy. Although all cases of nonseminomatous GCT were negative for tumor markers after cisplatin‐based chemotherapy, two cases showed variable GCT cells and two had somatic components (angiosarcoma and rhabdomyosarcoma) in resected specimens. Three relapsed soon after surgery. Growing teratoma syndrome developed during chemotherapy in four cases. Urgent thoracic surgery was performed in three patients, but one case was inoperable. The calculated 10‐year overall survival rates were 100% in mediastinal seminoma and 64.7% in NSGCT. During follow‐up, second non‐GCT malignancies developed in three patients (colon cancer, 190 months; thyroid cancer, 260 months; non‐small cell lung cancer, 250 months after the initial chemotherapy) and one patient with primary mediastinal seminoma was associated with multiple type I endocrine tumors. Conclusions: Our experiences demonstrated that long‐term survival and/or cure can be achieved with adequate chemotherapy followed by local surgical treatment even in patients with mediastinal GCTs. However, the clinical manifestations and biological behaviors during and/or after chemotherapy were complex and varied. In addition, the development of secondary malignancies should be taken into consideration for long‐term follow‐up. Clinicians should be aware of the various clinical features and secondary malignancies in primary mediastinal GCTs. [ABSTRACT FROM AUTHOR]

Tumor cells in extramammary Paget's disease sometimes overexpress human epidermal growth factor receptor 2 (HER2). Several case reports indicated successful response to HER2 inhibitor in patients with HER2‐positive metastatic extramammary Paget's disease. However, these were single‐case reports, and most cases were evaluated only by immunohistochemistry and treated with HER2 inhibitor monotherapy. Here, we report cases of HER2‐positive metastatic extramammary Paget's disease identified by both immunohistochemistry and in situ hybridization, and the patients were treated with HER2 inhibitor (trastuzumab) and paclitaxel combination chemotherapy. Partial response was observed in one case. The case was positive on both immunohistochemistry (3+) and in situ hybridization (HER2/chromosome 17 centromere, ≥2.0). Our observations suggest that HER2 should be checked in patients with advanced and/or metastatic extramammary Paget's disease, and that therapy with HER2 blockers should be considered as an option for treatment of HER2‐positive extramammary Paget's disease, especially in cases positive for both HER2 gene amplification and overexpression. [ABSTRACT FROM AUTHOR]

Ganglioneuroblastoma is an uncommon malignant tumor of the sympathetic nervous system, which is considered a disease of children with the majority of cases in patients less than four years old and it rarely occurs in adults. We encountered a very unusual case of a posterior mediastinal ganglioneuroblastoma that developed in a 17‐year‐old male adolescent who underwent successful excision of the mediastinal mass and remained stable postoperatively. However, he developed lumbago one year after the surgery. Radiographic findings revealed osteolytic lesions in the lumbar vertebra and histological analysis confirmed bone metastasis of ganglioneuroblastoma. Here, we report the clinical course and present a review of the literature regarding adolescent and adult onset mediastinal ganglioneuroblastoma. [ABSTRACT FROM AUTHOR]

A 32‐year‐old woman was referred to our hospital because of severe psychosis and was found to have an ectopic ACTH‐producing thymic neuroendocrine tumor. Laboratory data revealed an elevated serum cortisol and plasma ACTH level, hypokalemia, and metabolic alkalosis. Chest computed tomography (CT) revealed an anterior mediastinal mass and multiple pulmonary nodules. As the patient was unable to communicate because of her consciousness disturbance, she was managed with artificial ventilation and deep sedation. Metyrapone and potassium supplementation were administered, and steroid psychosis gradually improved. Thoracic surgery was performed and the histopathological diagnosis was thymic neuroendocrine tumor with positive anti‐ACTH immunohistochemical staining. Here we present details of the case and review the literature. [ABSTRACT FROM AUTHOR]

Background: Fluorine‐18‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) uptake in primary lesions has been well studied, but little information is available about metastatic bone lesions in patients with lung cancer. The present study was performed to evaluate the relationships between metastatic bone FDG uptake and clinical parameters in patients with lung cancer. Methods: FDG uptake was evaluated as the maximum standardized uptake (SUVmax) value of each targeted bone lesion, and the bone to primary lesion ratio of SUVmax (B/P ratio) was calculated. Forty‐nine patients (27 men and 22 women) with a diagnosis of lung cancer (small cell lung cancer [SCLC], n = 7; non‐small cell lung cancer [NSCLC], n = 42) with bone metastasis, and a total of 185 bone metastatic lesions were evaluated. Results: The SUVmax in bone and the B/P ratio were significantly higher in patients with pain and subsequent development of skeletal‐related events than in those without pain or skeletal‐related events, respectively. In addition, the SUVmax in metastatic bone lesions and the B/P ratio in SCLC were significantly lower than those in NSCLC, despite similar FDG uptake in the primary tumor. Conclusion: Our findings suggest that FDG‐PET evaluation in metastatic bone lesions could be useful to predict initial pain and subsequent clinical outcomes of local bone status in initially diagnosed lung cancer patients with bone metastasis. In addition, our results suggest that there could be histological differences in the biological activity of bone metastatic lesions in lung cancer, especially between SCLC and NSCLC. [ABSTRACT FROM AUTHOR]

Herein, we report a case of an angiosarcoma in a mediastinal non‐seminomatous germ cell tumor that exhibited growing teratoma syndrome during chemotherapy. A 26‐year‐old man presented with a giant anterior mediastinal mass, which was diagnosed as a non‐seminomatous germ cell tumor. The patient was administered three cycles of chemotherapy (bleomycin, etoposide, and cisplatin), but the mass grew despite normalization of tumor markers. Massive bleeding during thoracic surgery resulted in incomplete resection, and the mass was clinically and pathologically diagnosed as growing teratoma syndrome (only mature teratoma). The residual mass continued to grow, and complete resection was subsequently achieved after a detailed analysis of its vascular anatomy using angiography. The final pathological findings revealed angiosarcoma, which indicated a rare somatic type of mediastinal non‐seminomatous germ cell tumor. [ABSTRACT FROM AUTHOR]

Malignant peripheral nerve sheath tumor (MPNST) in the thorax is an extremely rare disease, and half of all cases of MPNST are associated with neurofibromatosis type I. Sporadic intrathoracic MPNST is difficult to diagnose and treat. Because of the rarity of intrathoracic MPNST, the optimal method of diagnosis and the efficacy of chemotherapy are unknown. Herein, we present a case of inoperable mediastinal MPNST, in which the diagnosis was immunohistochemically made by the loss of H3K27me3 expression in a transbronchial needle biopsy specimen. The patient showed a good response to doxorubicin plus ifosfamide chemotherapy. The present case highlights that MPNST should be included in the differential diagnosis of non-posterior mediastinum thoracic lesions, and that appropriate diagnosis and treatment for intrathoracic MPNST should be considered in patients with a thoracic mass. [ABSTRACT FROM AUTHOR]

Large granular lymphocyte leukemia ( LGL L) has been morphologically characterized as a group of lymphoproliferative diseases that include T-cell large granular lymphocytic leukemia (T- LGL L) and chronic lymphoproliferative disorders of natural killer cells ( CLPD- NK). We investigated mutations in the Src homology 2 ( SH2) domain of the signal transducer and activator of transcription 3 ( STAT3) gene in Asian cohorts of T- LGL L and CLPD- NK ( n = 42 and 11, respectively). Two mutations, Y640F and D661Y, were identified using direct sequencing or allele-specific ( AS) PCR. Y640F and D661Y mutations were found in seven and 18 patients, respectively. Two patients were positive for both mutations. Frequencies of STAT3 mutations in T- LGL L and CLPD- NK were 47.6% and 27.2%, respectively. Pure red cell aplasia ( PRCA) was associated with the mutations ( P = 0.005). The mutations were persistently found at stable levels in some patients after more than 5 years using AS-quantitative PCR. The results of the present study indicate that the SH2 domain of the STAT3 gene is frequently mutated in Asian T- LGL L and CLPD- NK, and that PRCA is closely correlated with the mutations. [ABSTRACT FROM AUTHOR]

Key message: This is the first report of a thymoma developing with unusual invasion into the oesophageal lumen. [ABSTRACT FROM AUTHOR]