Adipocyte-Like Differentiation in a Posttreatment Embryonal Rhabdomyosarcoma.

We describe a 16-year-old boy with rhabdomyosarcoma, consistent with embryonal subtype, of the lower extremity who received systemic neoadjuvant chemotherapy and subsequent excision. Microscopic sections of the postchemotherapy excision demonstrated diffuse, prominent, and immature adipocyte-like differentiation, in addition to skeletal muscle differentiation. Adipocyte-like differentiation was confirmed by a combination of positive Oil Red O and adipophilin immunohistochemical staining. To our knowledge, this represents the first report of an unusual phenomenon of differentiation of a soft tissue rhabdomyosarcoma into adipocyte-like cells after chemotherapy

Cutibacterium (formerly Propionibacterium) acnes clavicular infection.

Cutibacterium (formerly Propionibacterium) acnes13, 16 is a slow growing, gram-positive bacteria that is naturally found in higher concentrations as skin flora on the chest and back, as well as in other areas with greater numbers of hair follicles.25, 37 Most of the reported cases of C. acnes shoulder girdle infection follow arthroplasty surgery,18, 20, 26, 27, 32, 35 which then often requires debridement, administration of intravenous antibiotics, and surgical revision of the implanted device.12, 15, 21, 28-30 In a recent study, 56% of 193 shoulder revisions had a positive culture, 70% of which grew C. acnes.30 Despite the relatively common presumed association of C. acnes humeral osteomyelitis with prosthetic infection, infection of the scapula or clavicle secondary to C. acnes is rare.4, 23, 36 Osteomyelitis of the clavicle involving any organism is also an uncommon event that can arise spontaneously via presumed hematogenous spread, or secondary to open fractures or internal fixation.6, 33 The most commonly found organism in clavicular osteomyelitis is Staphylococcus aureus.9 We here report two cases of clavicular infection secondary to C. acnes that were not associated with implants

Cdkn2a (Arf) loss drives NF1-associated atypical neurofibroma and malignant transformation

Plexiform neurofibroma (PN) tumors are a hallmark manifestation of neurofibromatosis type 1 (NF1) that arise in the Schwann cell (SC) lineage. NF1 is a common heritable cancer predisposition syndrome caused by germline mutations in the NF1 tumor suppressor, which encodes a GTPase-activating protein called neurofibromin that negatively regulates Ras proteins. Whereas most PN are clinically indolent, a subset progress to atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP) and/or to malignant peripheral nerve sheath tumors (MPNSTs). In small clinical series, loss of 9p21.3, which includes the CDKN2A locus, has been associated with the genesis of ANNUBP. Here we show that the Cdkn2a alternate reading frame (Arf) serves as a gatekeeper tumor suppressor in mice that prevents PN progression by inducing senescence-mediated growth arrest in aberrantly proliferating Nf1−/− SC. Conditional ablation of Nf1 and Arf in the neural crest-derived SC lineage allows escape from senescence, resulting in tumors that accurately phenocopy human ANNUBP and progress to MPNST with high penetrance. This animal model will serve as a platform to study the clonal development of ANNUBP and MPNST and to identify new therapies to treat existing tumors and to prevent disease progression

Histopathologic findings in malignant peripheral nerve sheath tumor predict response to radiotherapy and overall survival

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive and poorly understood malignant neoplasm. Even in the setting of multimodal therapy, the clinical course of MPNST is frequently marked by metastatic conversion and poor overall prognosis, with optimal treatment paradigms for this rare tumor unknown. METHODS: We reviewed the medical records and histopathology of 54 consecutive patients who were treated at University of California San Francisco between 1990 and 2018. RESULTS: Our cohort consisted of 24 male and 30 female patients (median age 38 years). Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) sarcoma grading criteria segregated patients into groups with differences in overall survival (OS) ( CONCLUSIONS: Our results lend support to the FNCLCC sarcoma grading criteria as a prognostic scheme for MPNST, although few cases of grade 1 were included. Further, we identify increased Ki-67 labeling as a strong predictor of poor OS from MPNST. Finally, we identify a subset of MPNSTs with a predictive immunohistochemical profile that has improved local control with adjuvant radiotherapy. These data provide insights into the grading and therapy for patients with MPNST, although further studies are needed for independent validation

Irradiation of Nf1 mutant mouse models of spinal plexiform neurofibromas drives pathologic progression and decreases survival

Background: Genetically susceptible individuals can develop malignancies after irradiation of normal tissues. In the context of therapeutic irradiation, it is not known whether irradiating benign neoplasms in susceptible individuals promotes neoplastic transformation and worse clinical outcomes. Individuals with Neurofibromatosis 1 (NF1) are susceptible to both radiation-induced second malignancies and spontaneous progression of plexiform neurofibromas (PNs) to malignant peripheral nerve sheath tumors (MPNSTs). The role of radiotherapy in the treatment of benign neoplasms such as PNs is unclear. Methods: To test whether radiotherapy promotes neoplastic progression of PNs and reduces overall survival, we administered spinal irradiation (SI) to conditional knockout mouse models of NF1-associated PNs in 2 germline contexts: Nf1 fllfl ; PostnCre + and Nf1 fl/- ; PostnCre + . Both genotypes develop extensive Nf1 null spinal PNs, modeling PNs in NF1 patients. A total of 101 mice were randomized to 0 Gy, 15 Gy (3 Gy × 5), or 30 Gy (3 Gy × 10) of spine-focused, fractionated SI and aged until signs of illness. Results: SI decreased survival in both Nf1 fllfl mice and Nf1 fl/- mice, with the worst overall survival occurring in Nf1 fl/- mice receiving 30 Gy. SI was also associated with increasing worrisome histologic features along the PN-MPNST continuum in PNs irradiated to higher radiation doses. Conclusions: This preclinical study provides experimental evidence that irradiation of pre-existing PNs reduces survival and may shift PNs to higher grade neoplasms

Agglomeration in counter-current spray drying towers. Part A: Particle growth and the effect of nozzle height

Agglomeration of particles and droplets is critical to the operation of spray dryers, however it remains relatively unexplored. This paper studies the effect of the nozzle height on product properties, wall deposits and dryer conditions in a counter-current spray drying tower of detergent with a swirling air flow. The process efficiency is driven by changes in particle agglomeration. To interpret the results and facilitate the study of swirl towers, it is useful to subdivide these units according to the sources of growth in (a) spray region(s), (b) concentrated near-wall region(s) and (c) wall deposits. The particles formed are very heterogeneous and show a size-dependent composition. In this case, particle properties are driven by the separation of solid and liquid phases during atomization and the formation of a heterogeneous set of droplets. Agglomeration serves to homogenise the product and create a distinct source of porosity. The capacity and energy consumption of the dryer are also determined by the evolution of the particle size, as fine powder is elutriated from the tower top and coarse particles are removed from the product. When the nozzle is moved to lower positions in the tower the increased temperature near the spray suppresses agglomeration, however the residence time is shortened and ultimately it leads to creation of wet, coarse granules. An optimum location is found high enough to maintain the drying efficiency but sufficiently far from the top exit to minimise the loss of fine particles. In this way, a capacity ratio (i.e. product vs spray dried powder) C > 90% can be obtained and energy efficiency maximised