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Background: Patients with advanced type B3 thymoma and thymic carcinoma resistant to chemotherapy have few treatment options. We report the efficacy and safety results of the combination of the anti-PD-L1 inhibitor avelumab with the anti-angiogenesis drug axitinib in patients with advanced type B3 thymoma and thymic carcinoma. Methods: CAVEATT was a single-arm, multicentre, phase 2 trial, conducted in two Italian centres (the European Instituteof Oncology and the Humanitas Institute, Milan) in patients with histologically confirmed type B3 thymoma or thymic carcinoma, with advanced stage of disease who had progressed after at least one line of platinum-based chemotherapy. Previous treatment with an anti-angiogenesis drug was allowed but not with immune checkpoint inhibitors. Other inclusion criteria were age 18 years or older, an Eastern Cooperative Oncology Group performance status of 0–2, progressive disease, and presence of measurable disease according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Patients received avelumab 10 mg/kg intravenously every 2 weeks and axitinib 5 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was the centrally assessed overall response rate according to RECIST version 1.1. Patients who received at least one cycle of treatment and had at least one CT scan after treatment start at scheduled time point by protocol were judged assessable for response and were included in efficacy and safety analyses. This study is registered with EUDRACT, 2017–004048–38; enrolment is completed and follow-up is ongoing. Findings: Between April 22, 2019, and June 30, 2021, 32 patients were enrolled. 27 patients had a thymic carcinoma, three a type B3 thymoma, and two a mixed type B3 thymoma and thymic carcinoma. 29 (91%) of 32 patients had stage IVB disease and 13 (41%) of 32 had been pretreated with an anti-angiogenesis drug. 11 of 32 patients had an overall response; thus the overall response rate was 34% (90% CI 21–50); no patients had a complete response, 11 (34%) had a partial response, 18 (56%) had stable disease, and in two patients (6%) progressive disease was the best response. The most common grade 3 or 4 adverse event was hypertension (grade 3 in six [19%] of 32 patients). Four (12%) of 32 patients developed serious adverse events that were new-onset immune-related adverse events, including one grade 3 interstitial pneumonitis, one grade 4 polymyositis, and two grade 3 polymyositis. There were no treatment-related deaths. Interpretation: Avelumab combined with axitinib has promising anti-tumour activity and acceptable toxicity in patients with advanced type B3 thymoma and thymic carcinoma progressing after chemotherapy, and could emerge as a new standard treatment option in this setting. Funding: Pfizer.

Summary Background Schwannoma is a benign tumor arising from Schwann cells of the peripheral nerves. It is often asymptomatic and can develop in the retroperitoneum, mediastinum, head and neck region, and upper and lower extremities. Schwannoma of the abdominal wall is extremely rare, but differential diagnosis with malignant neoplasms is important to reduce the risk of undertreatment. Methods A narrative review of abdominal wall schwannoma was performed using PubMed, EMBASE, and Web of Science database and the search terms “schwannoma”, “neurinoma”, “neurilemmoma”, “soft tissue tumors”, “neurogenic tumor”, “rectus abdominis mass”, “abdominal wall”. In addition, the hospital charts were reviewed to report the personal experience. Results Only 9 single case-reports of benign schwannoma of the abdominal wall were found in the English medical literature over the past decade. None of the patients received preoperative biopsy and all were resected with clear margins. In addition to the literature review, we report the case of a 58-year-old man referred for a palpable mass in the left upper abdominal quadrant. Ultrasonography and magnetic resonance imaging revealed a solid and well-encapsulated mass inside the left rectus abdominis muscle. A core biopsy of the lesion provided the diagnosis of cellular schwannoma and this was confirmed by histopathologic examination of the surgical specimen. Conclusions Benign schwannoma of the abdominal wall is extremely rare. Percutaneous core needle biopsy is important for the differential diagnosis with more common and biologically more aggressive malignancies, such as desmoid tumors and sarcomas, and may be relevant for planning the most appropriate management.

Background Primary enteric adenocarcinoma of the thymus (EAT) is a recently proposed rare subtype of thymic carcinoma. Unlike thymic carcinomas with squamous histology, for which clinical guidelines are available, little knowledge is available regarding the clinical and pathological features of EAT, and there is no consensus on the best treatment algorithm for such tumors. Methods We performed a systematic review of the literature, searching for all cases of EAT reported. We also retrospectively reviewed all cases of EAT treated at the European Institute of Oncology (IEO) between January 2000 and January 2020. Individual patient data were extracted and analyzed in order to delineate clinical and pathological features, as well as patients’ prognosis and treatments outcome, evaluated in terms of Disease free Survival (DFS), Progression free survival (PFS) and overall survival (OS). Results Thirty-three cases (29 reported in literature and 4 new cases treated at IEO) of thymic adenocarcinoma deploying enteric differentiation as defined by WHO-criteria were analyzed. All tumors showed positive immunoreactivity for cytokeratin (CK) 20 and/or caudal type homeobox 2 (CDX2). Data on molecular profiling by next-generation sequencing were available in only 3 cases, and did not show actionable findings. At diagnosis, 11 pts had an early-stage (Masaoka I-II) and 22 a locally advanced (10 pts) or metastatic (12 pts) disease. Median-DFS of patients with localized disease was 12 months (95% CI, 7–19). Patients who received systemic chemotherapy were mostly treated with regimens commonly used for thymic epithelial tumors, with a discouraging PFS of 3–5 months for patients with stage IV disease. Median OS of the whole population was 34 months (95% CI, 24–NA:. mOS was not reached for patients with stage I-II disease versus 34 months in stage III-IV (p Conclusion Available evidence suggests that EAT represents a distinct entity in the context of thymic epithelial tumors, characterized by aggressive clinical behavior, poor responsiveness to chemotherapy and dismal patients prognosis. More research is needed to better define optimal management strategies for patients with such rare disease.

Neurofibromas are benign peripheral nerve sheath tumours, which are usually solitary and sporadic. Solitary neurofibromas of the breast are rare. The most common location of a breast neurofibroma is the nipple–areola complex. We report a rare case of a 56-year-old woman with a solitary neurofibroma of the right breast sulcus.

We investigated the relationship between the severity of histological inflammatory responses in the placenta, chorionic plate, and umbilical cord in conjunction with the intraventricular hemorrhage (IVH) risk in premature infants. Clinical data were prospectively collected for 287 consecutive premature neonates born before 32 completed weeks of gestation and admitted to the level III neonatal intensive care unit of the Department of Pediatrics at Padua University from January 1999 to December 2004. Placental histology for histological chorioamnionitis (HCA) was graded and scored according to Redline and others. The diagnosis of IVH (grades I–IV) was graded according to Volpe's classification. Among the placentas of the 287 preterm examined infants, 68 (23.6%) were diagnosed with acute HCA. Overall incidence of IVH was 11.8%. Of 68 preterm neonates with HCA, 11 developed IVH (16.1%). Maternal HCA at the higher grades and stages increased the risk of IVH: 7 (64%) of the 11 preterm infants with maternal HCA grade 3 developed IVH (RR; 95% CI 2.05; 1.1–3.6) and 8 (73%) of the 11 preterm neonates with stage 3 developed IVH (RR; 95% CI 1.59; 1.0–2.5). Conversely, fetal inflammation was not associated with an increased risk of IVH. In conclusion, the IVH risk in preterm infants at less than 32 gestation weeks is significantly associated with severe grade and stage maternal HCA inflammatory scores.

Myxoinflammatory fibroblastic sarcoma (MIFS) is a low-grade sarcoma generally arising in adults. We present a case of MIFS in a 5-year-old boy with a palpable nodule in the subcutaneous tissue of the scalp. We carried out a literature review to evaluate the diagnostic patterns based on histologic and cytologic features and possible pitfalls and misdiagnoses. A systematic search for articles of interest published between 1995 and 2011 was performed in MEDLINE and PubMed using the words “myxoinflammatory fibroblastic sarcoma,” “myxohyaline tumor,” and “inflammatory myxoid tumor.” Histology and cytology have a pivotal role in the differential diagnosis between MIFS and other potential soft-tissue mimics, such as nodular and proliferative fasciitis and inflammatory myofibroblastic tumor. Fine-needle aspiration cytology is a safe and useful tool for the diagnosis of pediatric patients with MIFS and is important for an accurate and precise preoperative workup to optimize subsequent management and treatment.

The diagnosis of malignant rhabdoid tumor (MRT) is straightforward if the typical, large eosinophilic rhabdoid cells are identified. We report on two diagnostically challenging cases of pediatric extra-renal MRTs which, when evaluated at incisional biopsy, were composed exclusively of small- to medium-sized round cells with focal spindling, lacking rhabdoid phenotype. This morphology, along with a polyphenotypic immunoprofile, including the expression of vimentin/CD99/cytokeratins/alpha-smooth muscle actin and vimentin/CD99/S-100 protein in case 1 and case 2, respectively, suggested the possibility of Ewing sarcoma (EWS)/PNET. However, molecular analyses failed to show the presence of the EWS/FLI-1 and EWS/ERG fusion transcripts, indicative of the most common translocations, i.e., t(11;22)(q24;q12) and t(22;21)(q22;q12), occurring in this tumor family. The revision of both cases included an immunohistochemical analysis with a commercially available anti-INI1 protein antibody. Immunohistochemistry, showing the absence of INI1 expression in neoplastic cells, strongly supported the diagnosis of MRT. Ultrastructural studies, performed on formalin-fixed tissues, were consistent with the diagnosis of MRT. This study suggests including anti-INI1 protein antibody in the immunohistochemical panel when evaluating pediatric tumors with ambiguous morphological and immunohistochemical features, particularly from small biopsies. A careful evaluation of clinical, pathological, and molecular findings is the key to a correct diagnostic approach of pediatric tumors.