Pseudomyogenic haemangioendothelioma (PHE) is an intermediate malignant vascular soft tissue tumour primarily affecting children and young adults. The molecular basis of this neoplasm is unknown. We here used chromosome banding analysis, fluorescence in situ hybridization (FISH), mRNA sequencing, RT-PCR and quantitative real-time PCR on a series of morphologically well-characterized PHEs to show that a balanced translocation, t(7;19)(q22;q13), detected as the sole cytogenetic aberration in two cases, results in fusion of the SERPINE1 and FOSB genes. This translocation has not been observed in any other bone or soft tissue tumour. Interphase FISH on sections from eight additional PHEs identified the same SERPINE1-FOSB fusion in all cases. The role of SERPINE1, which is highly expressed in vascular cells, in this gene fusion is probably to provide a strong promoter for FOSB, which was found to be expressed at higher levels in PHEs than in other soft tissue tumours. FOSB encodes a transcription factor belonging to the FOS family of proteins, which, together with members of the JUN family of transcription factors, are major components of the activating protein 1 (AP-1) complex. Further studies are needed to understand the cellular impact of the aberrant expression of the FOSB gene, but as the t(7;19) resulting in the SERPINE1-FOSB fusion seems to be pathognomonic for PHE, FISH or RT-PCR could be useful for differential diagnostic purposes.

Benign fibrous histiocytomas (FH) can be subdivided into several morphological and clinical subgroups. Recently, gene fusions involving either one of two protein kinase C genes (PRKCB and PRKCD) or the ALK gene were described in FH. We here wanted to evaluate the frequency of PRKCB and PRKCD gene fusions in FH. Using interphase fluorescence in situ hybridization on sections from formalin-fixed paraffin-embedded (FFPE) tumors, 36 cases could be analyzed. PRKCB or PRKCD rearrangements were seen in five tumors: 1/7 regular, 0/3 aneurysmal, 0/6 cellular, 2/7 epithelioid, 0/1 atypical, 2/10 deep, and 0/2 metastatic lesions. We also evaluated the status of the ALK gene in selected cases, finding rearrangements in 3/7 epithelioid and 0/1 atypical lesions. To assess the gene fusion status of FH further, deep sequencing of RNA (RNASeq) was performed on FFPE tissue from eight cases with unknown gene fusion status, as well as on two FH and six soft tissue sarcomas with known gene fusions; of the latter eight positive controls, the expected fusion transcript was found in all but one, while 2/8 FH with unknown genetic status showed fusion transcripts, including a novel KIRREL/PRKCA chimera. Thus, also a third member of the PRKC family is involved in FH tumorigenesis. We conclude that gene fusions involving PRKC genes occur in several morphological (regular, cellular, aneurysmal, epithelioid) and clinical (cutaneous, deep) subsets of FH, but they seem to account for only a minority of the cases. In epithelioid lesions, however, rearrangements of PRKC or ALK were seen, as mutually exclusive events, in the majority (5/7) of cases. Finally, the study also shows that RNA-Seq is a promising tool for identifying gene fusions in FFPE tissues. Benign fibrous histiocytoma (FH) can be subdivided into several morphological and clinical subgroups. Morphological variants include cellular, aneurysmal, epithelioid, and atypical types, and clinical manifestations range from benign tumors of the skin, deep soft tissues or skeleton to, rarely, metastasizing tumors. [1][2][3] We recently showed that both cutaneous and deep FH may carry specific gene fusions, in which a membereither PRKCB and PRKCD-of the gene family encoding protein kinase C (PRKC) is juxtaposed with a gene encoding a membrane-associated protein. 4 The pathogenetic mechanism was assumed to involve the uncoupling of the carboxy-terminal kinase domain of the PRKC protein from its regulatory domain, and its ectopic localization through fusion with the amino-terminal part of a membrane-associated protein. It has also recently been shown that some cases of epithelioid, and possibly also atypical, FH may harbor fusions activating the ALK protein. 5,6 The connection between ALK rearrangements and FH was further evaluated and strengthened by Doyle et al., showing that ALK fusions were restricted to the epithelioid subtype. 7 To study the frequency and distribution of PRKCB and PRKCD fusions in FH, we used interphase fluorescence in situ hybridization (FISH) on a series of tumors that...

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. Alveolar (ARMS) and embryonal (ERMS) histologies predominate, but rare cases are classified as spindle cell/sclerosing (SRMS). For treatment stratification, RMS is further subclassified as fusion-positive (FP-RMS) or fusion-negative (FN-RMS), depending on whether a gene fusion involving PAX3 or PAX7 is present or not. We investigated 19 cases of pediatric RMS using high resolution single-nucleotide polymorphism (SNP) array. FP-ARMS displayed, on average, more structural rearrangements than ERMS; the single FN-ARMS had a genomic profile similar to ERMS. Apart from previously known amplification (e.g., MYCN, CDK4, and MIR17HG) and deletion (e.g., NF1, CDKN2A, and CDKN2B) targets, amplification of ERBB2 and homozygous loss of ASCC3 or ODZ3 were seen. Combining SNP array with cytogenetic data revealed that most cases were polyploid, with at least one case having started as a near-haploid tumor. Further bioinformatic analysis of the SNP array data disclosed genetic heterogeneity, in the form of subclonal chromosomal imbalances, in five tumors. The outcome was worse for patients with FP-ARMS than ERMS or FN-ARMS (6/8 vs. 1/9 dead of disease), and the only children with ERMS showing intratumor diversity or with MYOD1 mutation-positive SRMS also died of disease. High resolution SNP array can be useful in evaluating genomic imbalances in pediatric RMS.

Aims To determine the rate of injuries related to cardiopulmonary resuscitation (CPR) in cardiac arrest non-survivors, comparing manual CPR with CPR performed using the Lund University Cardiac Assist System (LUCAS). Methods and results We prospectively evaluated 414 deceased adult patients using focused, standardized post-mortem investigation in years 2005 through 2013. Skeletal and soft tissue injuries were noted, and soft tissue injuries were evaluated with respect to degree of severity. We found sternal fracture in 38%, rib fracture in 77%, and severe soft tissue injury in 1.9% of cases treated with CPR with manual chest compressions (n = 52). Treatment with LUCAS CPR (n = 362) was associated with significantly higher rates of sternal fracture (80% of cases), rib fracture (96%), and severe soft tissue injury (10%), including several cases of potentially life-threatening injuries. Conclusion LUCAS CPR causes significantly more CPR-related injuries than manual CPR, while providing no proven survival benefit on a population basis. We suggest judicious use of the LUCAS device for cardiac arrest.

No abstract

Fine-needle aspiration cytology (FNAC) has been commonly used to follow up on previously treated sarcomas or to confirm soft tissue and bone metastases of carcinomas, melanomas or lymphomas. Its role as the firstline approach in the diagnosis of primary soft tissue and bone tumors has increased due to progress of less invasive diagnostic procedures and the growing availability of diagnostic ancillary tests.This comprehensive and richly-illustrated volume presents cytomorphology of all common neoplastic soft tissue and bone lesions but also of rare tumors largely described in case reports. Key points for cytological features, differential diagnosis, and the use of ancillary tests are discussed and illustrated in order to facilitate the diagnostic work-up in FNA samples.The volume is organized on the basis of the most recent WHO classification used in surgical pathology in order to provide a practical guide for modern cytologic diagnosis of surgical soft tissue and bone pathology. It is aimed mainly at surgical pathologists and cytopathologists, but also at orthopedic surgeons and clinical oncologists. CoNTeNTS

No abstract

We report a patient with severe anaphylactic shock immediately after injection of i.v. fluorescein. The patient recovered without sequela. Immunoglobulin E (IgE) mechanism was highly suggestive with significant increase in serum tryptase, positive basophil allergen threshold sensitivity (CD-sens) and histamine release tests towards fluorescein. This is, to our knowledge, the first report where CD-sens has been used to aid in diagnosing an IgE-mediated anaphylactic shock caused by fluorescein.