A woman in her 30s, non-smoker, presented at the emergency department two times because of spontaneous pneumothorax. The first episode was treated with small bore catheter drainage, while during the second episode—occurring only 1 week later—thoracoscopic talcage was attempted. The postoperative course was characterised by slow clinical and radiological resolution, and recurrence 3 days after discharge. Eventually, multiportal video-assisted thoracoscopic exploration identified an interfissural solid mass. Resection and further work-up revealed the diagnosis of ‘low-risk’ solitary fibrous tumour (SFT) stage pT1N0M0. The interdisciplinary tumour board advised no adjuvant therapy. A CT thorax was scheduled in 1 year for follow-up. The patient was discharged without complications and has had no recurrences of pneumothorax at 6 months of follow-up. This report shows that SFT can easily be missed on initial presentation and should be considered in the differential diagnosis of pneumothorax, especially when frequently recurring.

Lipomatous neoplasms are a rare entity in the pediatric population, comprising less than 10% of soft tissue tumors in the first two decades of life. Some characteristics of pediatric adipocytic tumors are analogous to their adult counterparts, some pediatric lipomatous lesions however harbor unique features. In recent years, there have been significant advances in the understanding of the pathogenesis and hence in the classification and treatment of pediatric adipocytic tumors. This literature-based article will provide a review of the presently known clinicopathological, immunohistochemical and molecular features of pediatric lipomatous lesions.

•Drug-induced valvular heart disease (DI-VHD) is reminiscent of carcinoid heart disease.•DI-VHD is mediated through 5-hydroxytryptamine 2β receptor signaling pathways.•Serotonergic agents interacting with this 2β receptor may cause carcinoid-like VHD.•DI-VHD must be considered in patients with no reasons for showing VHD and using SSRI.•Echocardiographic surveillance is warranted in patients on serotonergic drugs, including SSRI.

Strong and diffuse pan-tropomyosin receptor kinase (TRK) reactivity in the setting of paediatric spindle cell tumours can be a diagnostic challenge, considering pan-TRK is not entirely specific for infantile fibrosarcoma or NTRK-rearranged spindle cell neoplasms. Recently, we encountered a challenging case of a spindle cell/sclerosing rhabdomyosarcoma (SRMS) with strong and diffuse pan-TRK reactivity. In addition, we found a new YAP1-MAML2 fusion, to our knowledge not yet described in SRMS. Ethics approval was granted by the Medical Ethics Committee UGent/UZGent (5/10/2020, EC/088-2020/sds). Parents of a 1-year-old boy, with a history of a nodule in the musculus latissimus dorsi below the left scapula since birth, noticed recent growth of the mass. Magnetic resonance imaging (MRI) showed a heterogenic lesion (48×24×38 mm) compatible with an aggressive fibrous mesenchymal lesion. Additional computed tomography (CT) of the thorax and an ultrasound of the abdomen did not show other lesions, or arguments for distant metastases. A Tru-Cut needle biopsy of the lesion was performed. Microscopy showed a cellular proliferation of spindle cells arranged in intersecting long fascicles with focal herringbone growth pattern. Focal haemangiopericytoma-like areas were seen. The cellular spindle cell areas alternated with more fibrous/sclerosing regions (Fig. 1). The spindle cells had elongated, fusiform nuclei with small inconspicuous nucleoli and surrounding indistinct, eosinophilic cytoplasm. Mild cytonuclear atypia, occasional hyperchromatic nuclei and sporadic mitotic activity were noted. Tumour necrosis was absent. In the background, a few scattered lymphocytes were seen. Tadpole or strap cells were not observed. Immunohistochemistry showed diffuse and strong expression of desmin (Fig. 2A) and patchy positivity for smooth muscle actin (SMA). There was cytoplasmic staining for β-catenin. No immunoreactivity was present for S100, nuclear transducing-like enhancer of split 1 (TLE-1), CD34, CD31, ERG and factor VIII. Strong and diffuse cytoplasmic staining for pan-TRK (clone EPR17341; Roche Diagnostics, Australia) was observed (Fig. 2B), suggestive for the diagnosis of an infantile fibrosarcoma. However, targeted RNA sequencing did not show NTRK1, NTRK2 or NTRK3 fusions (Oncomine Focus Assay; ThermoFisher Scientific, USA). In addition, staining for MyoD1 showed diffuse and strong nuclear positivity (Fig. 2C). There was only focal nuclear positivity for myogenin (MYF4) (Fig. 2D).Fig. 2(A) Diffuse desmin positivity. (B) Pan-TRK showing cytoplasmic expression. (C) Diffuse and strong nuclear positivity for MyoD1. (D) Focal nuclear positivity for myogenin (MYF4).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Based on the spindle cell morphology with variable cytonuclear atypia and intersecting sclerous areas, the clinical presentation (infant with rapidly growing painless mass in head and neck region), as well as the immunohistochemical profile with rhabdomyoblastic differentiation, the diagnosis of SRMS was made. Next, additional bulk RNA sequencing (KAPA hyperprep with ribo-depletion; Roche) was performed, which revealed a YAP1-MAML2 gene fusion. MYOD1 mutations, or rearrangements/fusions of FOX01, NCOA2 or VGLL2 were not found. After biopsy, chemotherapy was started according to the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) rhabdomyosarcoma (RMS) 2005 protocol [group C = ifosfamide, vincristine, actinomycin D (IVA) ×9]. There was a good clinical response to the neoadjuvant chemotherapy with reduction in tumour size from 48 mm to 30 mm. After four IVA courses a surgical resection was performed. The post-treatment pathological specimen showed extensive fibrosis, inflammation and atrophic non-neoplastic skeletal muscle. Residual viable tumour cells were seen in 20% of the resected specimen. The resection margins were tumour free. The post-operative treatment was discussed with clinical experts in childhood RMS. It was decided to give six IVA courses instead of nine, to reduce the long-term toxicity of ifosfamide, followed by three vincristine and actinomycin D (VA) courses. The patient received his last treatment 6 months ago. He is currently in good clinical condition and disease free. Paediatric spindle cell tumours comprise a heterogeneous group of neoplasms spanning benign to malignant processes. Given the morphological overlap with other paediatric spindle cell tumours, SRMS can be a challenging diagnosis. The differential diagnosis of SRMS can be broad and includes infantile fibrosarcoma, desmoid-type fibromatosis, infantile myofibromatosis, fibrous hamartoma of infancy, lipofibromatosis and lipofibromatosis-like neural tumour.1Hung Y.P. Fletcher C.D.M. Hornick J.L. Evaluation of pan-TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis-like neural tumour and histological mimics.Histopathology. 2018; 73: 634-644Crossref PubMed Scopus (100) Google Scholar Due to the atypical spindle cell morphology with fascicular/herringbone pattern, the haemangiopericytoma-like vasculature, scattered lymphocytes in the background, and the strong and diffuse cytoplasmic pan-TRK staining, this case showed a striking resemblance to infantile fibrosarcoma. 1Hung Y.P. Fletcher C.D.M. Hornick J.L. Evaluation of pan-TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis-like neural tumour and histological mimics.Histopathology. 2018; 73: 634-644Crossref PubMed Scopus (100) Google Scholar There was no co-expression of CD34 and S100, making the diagnosis of a NTRK-rearranged spindle cell neoplasm/lipofibromatosis-like neural tumour less likely.2Suurmeijer A.J. Dickson B.D. Swanson D. et al.The histologic spectrum of soft tissue spindle cell tumors with NTRK3 gene rearrangements.Genes Chromosomes Cancer. 2019; 58: 739-746Crossref PubMed Scopus (52) Google Scholar However, diffuse pan-TRK immunoreactivity, a highly sensitive diagnostic marker for infantile fibrosarcoma and NTRK-rearranged spindle cell neoplasm, is not entirely specific and has been described in a subset of paediatric spindle-cell tumours including infantile myofibromatosis and fibrous hamartoma of infancy.1Hung Y.P. Fletcher C.D.M. Hornick J.L. Evaluation of pan-TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis-like neural tumour and histological mimics.Histopathology. 2018; 73: 634-644Crossref PubMed Scopus (100) Google Scholar To the best of our knowledge, pan-TRK immunoreactivity has been described in only one case of SRMS.1Hung Y.P. Fletcher C.D.M. Hornick J.L. Evaluation of pan-TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis-like neural tumour and histological mimics.Histopathology. 2018; 73: 634-644Crossref PubMed Scopus (100) Google Scholar Due to the diffuse desmin positivity in this case, MyoD1 and myogenin stainings were performed which led to the diagnosis of an infantile SRMS. Moreover, morphological rhabdomyoblastic differentiation (presence of rhabdomyoblasts with elongated eosinophilic tails with cross striations, so-called tadpole or strap cells) is not detectable in most SRMS (similar to the current case), making the diagnosis of SRMS even more challenging. SRMS is a subtype of RMS and can be divided into three genomic groups. The first group, the congenital/infantile spindle cell rhabdomyosarcoma, shows gene fusions involving the VGLL2 and NCOA2 genes. The gene fusions include SRF-NCOA2, TEAD1-NCOA2, VGLL2-NCOA2, and VGLL2-CITED2. The second group of SRMS, more common in adolescents and young adults, is characterised by a MYOD1 gene mutation. The third group of SRMS has not shown recurrent identifiable genetic alterations until now.3Agaram N.P. Szuhai K. Spindle cell/sclerosing rhabdomyosarcoma.in: WHO Classification of Tumours Editorial Board. WHO Classification of Soft Tissue and Bone Tumours. 5th ed. IARC Press, Lyon2020Google Scholar,4Alaggio R. Zhang L. Sung Y. et al.A molecular study of pediatric spindle and sclerosing rhabdomyosarcoma: identification of novel and recurrent VGLL2-related fusions in infantile cases.Am J Surg Pathol. 2016; 40: 224-235Crossref PubMed Scopus (123) Google Scholar Due to this subclassification with different biological behaviour, additional molecular analysis was performed.4Alaggio R. Zhang L. Sung Y. et al.A molecular study of pediatric spindle and sclerosing rhabdomyosarcoma: identification of novel and recurrent VGLL2-related fusions in infantile cases.Am J Surg Pathol. 2016; 40: 224-235Crossref PubMed Scopus (123) Google Scholar,5Agaram N.P. LaQuaglia M.P. Alaggio R. et al.MYOD1-mutant spindle cell and sclerosing rhabdomyosarcoma: an aggressive subtype irrespective of age. A reappraisal for molecular classification and risk stratification.Mod Pathol. 2019; 32: 27-36Crossref PubMed Scopus (75) Google Scholar Bulk RNA revealed a YAP1-MAML2 fusion [YAP1 (NM_001282101.1) exon 5 – MAML2 (NM_032427.3) exon 2] instead of NTRK, VGLL2 and NCOA2 fusions, and showed no MYOD1 mutations. In conclusion, we present a challenging case of a rare infantile SRMS with a novel fusion gene and an unexpected strong and diffuse pan-TRK reactivity, strikingly mimicking infantile fibrosarcoma and other paediatric spindle cell tumours. Strong and diffuse pan-TRK reactivity in the setting of paediatric spindle cell tumours is apparently not entirely specific for infantile fibrosarcoma or NTRK-rearranged spindle cell neoplasms; hence, molecular testing/confirmation is strongly advised in these cases. If confronted with paediatric spindle cell lesions with desmin positivity, even in the absence of clear morphological rhabdomyoblastic differentiation, it is recommended to perform additional immunohistochemical stainings for rhabdomyoblastic differentiation (in particular MyoD1 which is more sensitive than myogenin) to confirm/exclude SRMS. Finally, using bulk RNA sequencing, we found a YAP1-MAML2 fusion in this case. Recurrent YAP1-MAML2 fusions have been reported in poroma and porocarcinoma,6Sekine S. Kiyone T. Ryo E. et al.Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma.J Clin Invest. 2019; 130: 3827-3832Crossref PubMed Scopus (67) Google Scholar and more recently in metaplastic thymoma,7Vivero M. Davineni P. Nardi V. et al.Metaplastic thymoma: a distinctive thymic neoplasm characterized by YAP1-MAML2 gene fusions.Mod Pathol. 2020; 33: 560-565Crossref PubMed Scopus (25) Google Scholar and retiform and composite haemangioendothelioma.8Antonescu C.R. Dickson B.C. Sung Y.S. et al.Recurrent YAP1 and MAML2 rearrangements in retiform and composite hemangioendothelioma.Am J Surg Pathol. 2020; 44: 1677-1684Crossref PubMed Scopus (21) Google Scholar To our knowledge, YAP1-MAML2 fusions have not previously been described in SRMS. We would like to thank Uta Flucke, Patrick Pauwels and Lennart Kester for their valuable technical support. The authors state that there are no conflicts of interest to disclose.

Background Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a systemic inflammatory process predominantly affecting upper and lower respiratory tract and kidneys. Valvular heart disease is a rare manifestation of GPA. Case summary We report two cases of acute valvular heart disease mimicking acute endocarditis caused by GPA. Both patients were middle-aged females with acute aortic valve regurgitation suggestive of possible infective endocarditis. In their recent medical history, atypical otitis and sinusitis were noted. The first patient was admitted with heart failure and the second patient because of persisting fever. Echocardiogram revealed severe aortic regurgitation with an additional structure on two cusps, suggestive of infective endocarditis in both patients. Urgent surgical replacement was performed; however, intraoperative findings did not show infective endocarditis, but severe inflammatory changes of the valve and surrounding tissue. In both patients, the valve was replaced by a prosthetic valve. Microscopic examination of the valve/myocardial biopsy showed diffuse acute and chronic inflammation with necrosis and necrotizing granulomas, compatible with GPA after infectious causes were excluded. Disease remission was obtained in both patients, in one patient with Rituximab and in the other with Glucocorticoids and Cyclophosphamide. Both had an uneventful follow-up. Discussion Granulomatosis with polyangiitis can be a rare cause of acute aortic valve regurgitation mimicking infective endocarditis with the need for surgical valve replacement. Atypical ear, nose, and throat symptoms can be a first sign of GPA. Symptom recognition is important for early diagnosis and appropriate treatment to prevent further progression of the disease.

Pancreatic nodules are frequently found incidentally and often pose a diagnostic and therapeutic challenge when surgery is considered. We present the case of a 66-year-old cirrhotic patient with a pancreatic nodule with signal intensity and contrast enhancement pattern suggestive for a non-functional neuroendocrine lesion. A (68)Gallium-DOTATOC PET-CT scan revealed a correspondent focal tracer uptake in the pancreatic tail. After distal pancreatectomy, the specimen surprisingly revealed intrapancreatic splenic tissue. Nuclear imaging has previously been reported to produce a false-positive result for the presence of a neuroendocrine tumor when an intrapancreatic accessory spleen is present. This case reminds us of the diagnostic pitfalls in pancreatic nodules, to consider a broad differential diagnosis and to remain critical before referring the patient for surgery.