Multiple non-ossifying fibromas as a cause of pathological femoral fracture in Jaffe-Campanacci syndrome.

BACKGROUND: Jaffe-Campanacci is a rare syndrome characterised by the association of café-au-lait spots, axillary freckles, multiple non-ossifying fibromas of the long bones and jaw, as well as some features of type 1 neurofibromatosis. There are less than 30 reported cases, and a genetic profile has not yet been determined. Furthermore, it has not been clarified whether it is a subtype of type 1 neurofibromatosis or a separate syndrome. The risk of pathological fracture is over 50%, due to substantial cortical thinning of the weight-bearing bones. CASE PRESENTATION: A 17-year-old female patient, known for type 1 neurofibromatosis, presented with a low-energy distal femoral fracture due to disseminated large non-ossifying fibromas. Investigations revealed all of the distinctive signs of Jaffe-Campanacci syndrome. Both her distal femurs and proximal tibias exhibited multiple non-ossifying fibromas. The fracture was treated by open reduction and internal plate fixation. Some of the bony lesions were biopsied to confirm the diagnosis. The fracture healed eventless, as did the lesions biopsied or involved in the fracture. The other ones healed after curettage and bone grafting performed at the time of plate removal. CONCLUSION: Jaffe-Campanacci is a rare syndrome having unclear interactions with type 1 neurofibromatosis, which still needs to be characterised genetically. It is associated with a high risk of pathological fracture, due to the presence of multiple large non-ossifying fibromas of the long bones, with an expected normal healing time. Curettage and bone grafting promote healing of the lesions and should be considered to prevent pathological fracture. We agree with other authors that all patients with newly-diagnosed type 1 neurofibromatosis should undergo an osseous screening to detect disseminated non-ossifying fibromas, and evaluate the inherent risk of pathological fracture

Tumor-Derived Mesenchymal Stem Cells Use Distinct Mechanisms to Block the Activity of Natural Killer Cell Subsets.

Mesenchymal stem cells (MSCs) display pleiotropic functions, which include secretion of soluble factors with immunosuppressive activity implicated in cancer progression. We compared the immunomodulatory effects on natural killer (NK) cells of paired intratumor (T)- and adjacent non-tumor tissue (N)-derived MSCs from patients with squamous cell lung carcinoma (SCC). We observed that T-MSCs were more strongly immunosuppressive than N-MSCs and affected both NK function and phenotype, as defined by CD56 expression. T-MSCs shifted NK cells toward the CD56 <sup>dim</sup> phenotype and differentially modulated CD56 <sup>bright/dim</sup> subset functions. Whereas MSCs affected both degranulation and activating receptor expression in the CD56 <sup>dim</sup> subset, they primarily inhibited interferon-γ production in the CD56 <sup>bright</sup> subset. Pharmacological inhibition of prostaglandin E2 (PGE2) synthesis and, in some MSCs, interleukin-6 (IL-6) activity restored NK function, whereas NK cell stimulation by PGE2 alone mimicked T-MSC-mediated immunosuppression. Our observations provide insight into how stromal responses to cancer dampen NK cell activity in human lung SCC

Differentiation of Crystals Associated With Arthropathies by Spectral Photon-Counting Radiography: A Proof-of-Concept Study.

The aims of this study were to test whether spectral photon-counting radiography (SPCR) is able to identify and distinguish different crystals associated with arthropathies in vitro and to validate findings in a gouty human third toe ex vivo. Industry-standard calibration rods of calcium pyrophosphate, calcium hydroxyapatite (HA), and monosodium urate (MSU) were scanned with SPCR in an experimental setup. Each material was available at 3 different concentrations, and a dedicated photon-counting detector was used for SPCR, whereas validation scans were obtained on a clinical dual-energy computed tomography (DECT) scanner. Regions of interest were placed on SPCR images and consecutive DECT images to measure x-ray attenuation characteristics, including effective atomic numbers (Zeff). Statistical tests were performed for differentiation of Zeff between concentrations, materials, and imaging modalities. In addition, a third toe from a patient with chronic gouty arthritis was scanned with SPCR and DECT for differentiation of MSU from HA. In both SPCR and DECT, significant differences in attenuation and Zeff values were found for different concentrations among (P < 0.001) and between different materials (P < 0.001). Overall, quantitative measurements of Zeff did not differ significantly between SPCR- and DECT-derived measurements (P = 0.054-0.412). In the human cadaver toe, gouty bone erosions were visible on standard grayscale radiographic images; however, spectral image decomposition revealed the nature and extent of MSU deposits and was able to separate it from bone HA by Zeff. Identification and differentiation of different crystals related to arthropathies are possible with SPCR at comparable diagnostic accuracy to DECT. Further research is needed to assess diagnostic accuracy and clinical usability in vivo

Cytology of Primary Salivary Gland-Type Tumors of the Lower Respiratory Tract: Report of 15 Cases and Review of the Literature.

Primary pulmonary salivary gland-type tumors are rare neoplasms arising from the seromucinous submucosal glands of the lower respiratory tract (LRT), the most common of which are mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma. They are morphologically indistinguishable from their salivary gland counterpart and recognizing them is a challenge, especially on cytological specimens. We analyzed 15 cases of histologically proven primary salivary gland tumors of the LRT to identify cytomorphological features and define potential diagnostic clues that might assist cytopathologists in the preoperative diagnosis of these neoplasias. Three out of the four cases of adenoid cystic carcinomas showed the characteristic tridimensional cell clusters and hyaline globules, whereas the last one did not show malignant cells; only two cases of MEC presented the three characteristic cell types (i.e., squamous, intermediate, and mucin secreting) on cytology. Since these neoplasms are rare and do not have a completely specific set of cytological features, it is important for practicing cytopathologists to be aware of the possibility of encountering them, in specimens from patients with LRT masses, in order to render the correct diagnosis

The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma.

Expression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not β-catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking β-catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation

Relationship between pneumonitis induced by immune checkpoint inhibitors and the underlying parenchymal status: a retrospective study.

In patients with primary or secondary lung tumour treated with immune checkpoint inhibitors, immune-related pneumonitis is a rare adverse event but may evolve to respiratory failure. Prompt management is required and usually consists of treatment interruption and immunosuppressive drug administration. The aim of this study was to evaluate relationships between immune-related pneumonitis and pre-existing parenchymal status, especially tumour location and history of chest radiotherapy. Computed tomography (CT) scans of patients with immune-related pneumonitis were retrospectively reviewed. Pattern, distribution and extent of pneumonitis were assessed in six lung regions. In patients who received radiotherapy, the extent of pneumonitis was evaluated according to the radiation field. Among 253 patients treated with immunotherapy, 15 cases of immune-related pneumonitis were identified. 10 had previous or concomitant chest radiotherapy in addition to immunotherapy. At CT scan, 29 (33%) out of 88 regions encompassed the primary tumour (n=4), a lung metastasis (n=4) and/or radiation fields (n=21). A significantly higher prevalence of parenchymal involvement by immune-related pneumonitis occurred within areas of primary or metastatic malignancy and/or radiation field (97%) as compared to other areas (3%, p=0.009). Lung regions affected by the primary tumour, metastasis or radiotherapy had a higher probability of immune-related pneumonitis than others (OR 10.8, p=0.024). An organising pneumonia (OP) pattern was more frequent after radiotherapy (70% versus 0%, p=0.024), whereas nonspecific interstitial pneumonia features were more commonly seen in radiotherapy-naive patients (100% versus 10%, p=0.002). In patients with primary or secondary lung tumour treated with immune checkpoint inhibitors, immune-related pneumonitis is preferentially located within lung areas involved by tumour and/or radiation fields

Imaging features and differential diagnoses of non-neoplastic diffuse mediastinal diseases.

Acute or chronic non-neoplastic diffuse mediastinal diseases have multiple causes, degrees of severity, and a wide range of management. Some situations require emergency care while others do not need specific treatment. Although the diagnosis may be suspected on chest X-ray, it is mainly based on CT. A delayed recognition is not uncommonly observed. Some findings may prompt the radiologist to look for specific associated injuries or lesions.This pictorial review will successively describe the various non-neoplastic causes of diffuse mediastinal diseases with their typical findings and major differentials.First, pneumomediastinum that can be provoked by extra- or intra-thoracic triggers requires the knowledge of patient's history or recent occurrences. Absence of any usual etiological factor should raise suspicion of cocaine inhalation in young individuals.Next, acute mediastinitis may be related to post-operative complications, esophageal perforation, or contiguous spread of odontogenic or retropharyngeal infections. The former diagnosis is not an easy task in the early stage, owing to the similarities of imaging findings with those of normal post-operative appearance during the first 2-3 weeks.Finally, fibrosing mediastinitis that is linked to an excessive fibrotic reaction in the mediastinum with variable compromise of mediastinal structures, in particular vascular and airway ones. Differential diagnosis includes tumoral and inflammatory infiltrations of the mediastinum

Conidiobolus pachyzygosporus invasive pulmonary infection in a patient with acute myeloid leukemia: case report and review of the literature.

Conidiobolus spp. (mainly C. coronatus) are the causal agents of rhino-facial conidiobolomycosis, a limited soft tissue infection, which is essentially observed in immunocompetent individuals from tropical areas. Rare cases of invasive conidiobolomycosis due to C. coronatus or other species (C.incongruus, C.lamprauges) have been reported in immunocompromised patients. We report here the first case of invasive pulmonary fungal infection due to Conidiobolus pachyzygosporus in a Swiss patient with onco-haematologic malignancy. A 71 year-old female was admitted in a Swiss hospital for induction chemotherapy of acute myeloid leukemia. A chest CT performed during the neutropenic phase identified three well-circumscribed lung lesions consistent with invasive fungal infection, along with a positive 1,3-beta-d-glucan assay in serum. A transbronchial biopsy of the lung lesions revealed large occasionally septate hyphae. A Conidiobolus spp. was detected by direct 18S rDNA in the tissue biopsy and subsequently identified at species level as C. pachyzygosporus by 28S rDNA sequencing. The infection was cured after isavuconazole therapy, recovery of the immune system and surgical resection of lung lesions. This is the first description of C. pachyzygosporus as human pathogen and second case report of invasive conidiobolomycosis from a European country

Abscopal effect in a patient with malignant pleural mesothelioma treated with palliative radiotherapy and pembrolizumab.

The abscopal effect describes the ability of locally administered radiotherapy to induce systemic antitumor effects. Although mentioned for the first time in the 1950s, records of abscopal effects, considered to be immune-mediated, are scarce with radiotherapy alone. However, with the continued development and use of immunotherapy, reports on the abscopal effect have become increasingly frequent during the last decade. Here, we report a patient with advanced malignant pleural mesothelioma who had progressive disease while on the anti-PDL1 inhibitor pembrolizumab and showed an abscopal response after palliative radiotherapy