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Background Since 2010, nationwide networks of reference centers for sarcomas (RREPS/NETSARC/RESOS) collected and prospectively reviewed all cases of sarcomas and connective tumors of intermediate malignancy (TIM) in France. Methods The nationwide incidence of sarcoma or TIM (2013–2016) was measured using the 2013 WHO classification and confirmed by a second independent review by expert pathologists. Simple clinical characteristics, yearly variations and correlation of incidence with published clinical trials are presented and analyzed. Results Over 150 different histological subtypes are reported from the 25172 patients with sarcomas (n = 18712, 74,3%) or TIM (n = 6460, 25.7%), with n = 5838, n = 6153, n = 6654, and n = 6527 yearly cases from 2013 to 2016. Over these 4 years, the yearly incidence of sarcomas and TIM was therefore 70.7 and 24.4 respectively, with a combined incidence of 95.1/106/year, higher than previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of tumors. Only GIST, as a single entity had a yearly incidence above 10/106/year. There were respectively 30, 64 and 66 different histological subtypes of sarcomas or TIM with an incidence ranging from 10 to 1/106, 1–0.1/106, or < 0.1/106/year respectively. The 2 latter incidence groups represented 21% of the patients with 130 histotypes. Published phase III and phase II clinical trials (p−6) are significantly higher with sarcomas subtypes with an incidence above 1/106 per. Conclusions This nationwide registry of sarcoma patients, with exhaustive histology review by sarcoma experts, shows that the incidence of sarcoma and TIM is higher than reported, and that tumors with a very low incidence (16/year) are less likely to be included in clinical trials.

International audience; Here we report the case of a 3-year-old child who had an intramuscular hemangioma presenting as a rapidly growing mass.

Background: Since 2010, presentation to a designated sarcoma tumor board and pathological review by an expert network are mandatory for sarcoma patients in France. NETSARC+ (merging the 3 initial RREPS, RESOS & NETSARC) collected prospectively all cases of reviewed sarcomas and tumors of intermediate malignancy (TIM) nationwide. We report on the incidence of subtypes according to WHO classification from 2013 to 2016. Methods: Sarcoma or TIM confirmed by review of expert sarcoma pathologists were all prospectively integrated in the database; the results using the latest WHO classification are presented for the years 2013 to 2016, including yearly variations. Correlation of the incidence of each histotype with dedicated published clinical trials was conducted. Results: 139 different histological subtypes are reported among the 25172 patients with sarcomas (n = 18710, 64%) or TIM (n = 6460, 36%), respectively n = 5838, n = 6153, n = 6654, and n = 6527 yearly from 2013 to 2016. Over these 4 years, the observed yearly incidence of sarcomas, TIM, and both was therefore 79.7, 24.9 and 95.1/106/year, above that previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of all sarcomas. Only GIST, as a single entity exceeded a yearly incidence above 10/million per year. There were respectively 30, 63 and 66 different histological subtypes of sarcomas or TIM (single entities or lumped together, e.g. MPNST, or vascular sarcomas...) with an incidence ranging from 10 to 1/106/year, 1-0.1/106 per year, or < 0.1/106/year respectively. The 2 later “incidence groups” included 21% of the patients. The incidence of 8 histotypes varied significantly over this 4 years. Patients with tumors with an incidence above 1/106 per year have significantly higher numbers of dedicated published phase III and phase II clinical trials (p < 10-6). Conclusions: This nationwide registry of sarcoma patients with an histology reviewed by sarcoma experts shows that the incidence of sarcoma and TIM is higher than previously reported, may vary over years for some histotypes, and that tumors with an incidence < 10e6 have a much lower access to clinical trials. Funding Statement: NetSARC (INCA & DGOS) and RREPS (INCA & DGOS), RESOS (INCA & DGOS) and LYRICAN (INCA-DGOSINSERM 12563), Institut Convergence PLASCAN (17-CONV-0002), Association DAM’s, Ensemble contre Le GIST, Eurosarc (FP7-278742), la Fondation ARC, Infosarcome, InterSARC (INCA), LabEx DEvweCAN (ANR-10-LABX-0061), Ligue de L’Ain contre le Cancer, La Ligue contre le Cancer, EURACAN (EC 739521) funded this study. Declaration of Interests: The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Plaque-like myofibroblastic tumor of infancy was first characterized in 2007 by Clarke et al. In the first 2 cases described, large plaque-like tumors presented in the first 3 months of life exhibited microscopic features consistent with dermatofibroma but with immunohistochemical features of myofibroblastic lineage. In 2013, Marqueling et al reported 3 additional cases, 2 of which presented in early childhood, prompting the authors to recommend that the name of this condition be shortened to plaque-like myofibroblastic tumor. We present here 4 additional cases to better characterize clinical and histopathological features of this newly recognized entity. This benign lesion is of myofibroblastic lineage and demonstrates features consistent with multiple clustered dermatofibroma.

11560 Background: Since 2010, presentation to a designated sarcoma tumor board and pathological review by an expert network are mandatory for sarcoma patients in France. NETSARC+ (merging the 3 initial RREPS, RESOS & NETSARC) collected prospectively all cases of reviewed sarcomas and tumors of intermediate malignancy (TIM) nationwide. We report on the incidence of subtypes according to WHO classification from 2013 to 2016. Methods: Sarcoma expert pathologists reviewed samples were all prospectively integrated in the database; the results using the latest WHO classification are presented for the years 2013 to 2016, including yearly variations. Correlation of the incidence of each histotype with dedicated published clinical trials was conducted. Results: 139 different histological subtypes are reported among the 25172 patients with sarcomas (n = 18710, 64%) or TIM (n = 6460, 36%), respectively n = 5838, n = 6153, n = 6654, and n = 6527 yearly from 2013 to 2016. Over these 4 years, the observed yearly incidence of sarcomas, TIM, and all was therefore 79.7, 24.9 and 95.1/10e6/year, above that previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of all sarcomas. Only GIST, as a single entity exceeded a yearly incidence above 10/million per year. There were respectively 30, 63 and 66 different histological subtypes of sarcomas or TIM (single entities or lumped together, e.g. MPNST, or vascular sarcomas...) with an incidence ranging from 10 to 1/10e6/year, 1-0.1/10e6 per year, or < 0.1/10e6/year respectively. The 2 later “incidence groups” included 21% of the patients. The incidence of 8 histotypes varied significantly over this 4 years. Patients with tumors with an incidence above 1/10e6 per year have significantly higher numbers of dedicated published phase III and phase II clinical trials (p < 10e-6). Conclusions: This nationwide registry of sarcoma patients with an histology reviewed by sarcoma experts shows that the incidence of sarcoma and TIM is higher than previously reported, may vary over years for some histotypes, and that tumors with an incidence < 10e6 have a much lower access to clinical trials.

International audience; No gold standard exists for histopathological diagnosis of a prosthetic joint infection (PJI). The historical criterion considers the presence of neutrophil infiltration upon examination of periprosthetic tissue. Morawietz et al. proposed a classification of periprosthetic membranes (Morawietz et al., Clin Pathol 59:591-597, 2006, https://doi.org/10.1136/jcp.2005.027458) and a more recently described classification with a new cutoff value of 23 neutrophils in 10 high-power fields (Morawietz et al., Histopathology 54:847-853, 2009. https://doi.org/10.1111/j.1365-2559.2009.03313.x). We performed a multicenter prospective study, which compared both methods for the diagnosis of PJI. All suspicions of PJI ( = 264) between December 2010 and March 2012 in seven centers were prospectively included. Five perioperative specimens were collected per patient for cultures, and one was collected for histology. Diagnosis of PJI was made according to the Infectious Diseases Society of America (IDSA) guidelines. Histopathological analysis classified the patients according to the threshold of 23 neutrophils and according to the classification of Morawietz. Performances of both methods were compared by using clinical and/or bacteriological criteria as the gold standard. Among 264 patients with suspected PJI, a diagnosis of infection was confirmed in 215 and unconfirmed in 49 patients. Histopathological analysis was available for 150 confirmed PJI and 40 unconfirmed PJI cases. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 78.7%, 90.0%, 96.7%, 52.9%, and 81.1%, respectively, for the Morawietz classification, and 82.0%, 90.0%, 96.9%, 57.1%, and 83.7%, respectively, for the 23-neutrophil threshold. The new algorithm using a threshold of 23 neutrophils can be proposed as a new gold standard for the histopathological diagnosis of PJI.

To assess the diagnostic value of ultrasound-guided (US-guided) synovial biopsy in routine clinical practice in cases of acute and chronic arthritis. A retrospective, single-center study of US-guided synovial biopsies between 2003 and 2013. The clinical, laboratory, radiographic, synovial fluid, and histological and bacteriological results of synovial biopsies were analyzed. Arthritis was classified according to disease duration

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International audience; Portal vein leiomyosarcoma (LMS) is a very rare entity with poor prognosis. Only few cases have been reported in the literature. We report the case of a 53-year-old man with portal vein LMS presenting as a hilar tumor and causing cholestasis. The tumor measured 10 cm and was responsible for right portal vein thrombosis and compression of the biliary convergence. A right hepatectomy with hilar en bloc resection was performed with portal vein and biliary reconstruction. Pathology confirmed the complete resection of a well-differentiated leiomyosarcoma of the portal vein. The postoperative outcome was uneventful and the patient received no adjuvant treatment. Six months after the procedure, the patient is doing well with a normal quality of life and without any sign of recurrence. Aggressive and radical surgery should be proposed in first intention for the treatment of portal vein LMS.

International audience; The differential diagnosis between atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) and dedifferentiated liposarcoma (DDLPS) from their morphologic counterparts is challenging. Currently, the diagnosis is guided by MDM2 and CDK4 immunohistochemistry (IHC) and is confirmed by the amplification of the corresponding genes. Recently, p16 IHC has been proposed as a useful diagnostic biomarker. The objective was to assess the utility of p16 IHC in the differential diagnosis of ALT/WDLPS and DDLPS. Our series included 101 tumors that were previously analyzed using fluorescence in situ hybridization for MDM2 and CDK4 amplification. We compared sensitivity and specificity of p16 IHC to MDM2 and CDK4 IHC in the differential diagnosis of ALT-WDLPS (n=19) versus benign adipocytic tumors (n=44) and DDLPS (n=18) versus mimicking sarcomas (n=20). In the differential diagnosis of ALT-WDLPS, p16 had a sensitivity of 89.5% but a specificity of 68.2%, which was impaired by false-positive lipomas with secondary changes, especially in biopsies. Likewise, in the differential diagnosis of DDLPS, p16 had a sensitivity of 94.4% and a specificity of 70%, which hampered its use as a single marker. However, adding p16 to MDM2 and/or CDK4 increased diagnostic specificity. Indeed, MDM2+/p16+ tumors were all ALT-WDLPS, and MDM2-/p16- tumors were all benign adipocytic tumors. Moreover, all MDM2+/CDK4+/p16+ tumors were DDLPS, and the MDM2-/CDK4-/p16- tumor was an undifferentiated sarcoma. Although the use of p16 as a single immunohistochemical marker is limited by its specificity, its combination with MDM2 and CDK4 IHC may help discriminate ALT-WDLPS/DDLPS.

Resume Objectifs La famille des kinases Aurora a un role crucial dans la regulation de la mitose. La surexpression d’Aurora A et B a ete rapportee dans de nombreux cancers. L’objectif de cette etude etait d’analyser l’expression d’Aurora A et B dans le carcinome a cellules renales (CCR) et son association avec les parametres cliniques et pathologiques usuels. Methodes Nous avons etudie retrospectivement des echantillons tumoraux de 40 patients operes pour tumeur renale entre 2003 et 2006. L’ARN etait extrait des echantillons tumoraux congeles correspondants. Apres controle de la qualite de l’ARN, 31 echantillons ont ete retenus afin d’evaluer l’expression des genes Aurora A et B par RTPCR. Une analyse statistique a ete realisee utilisant le test du χ 2 afin de comparer les niveaux d’expression d’Aurora A et B. Resultats L’âge moyen des patients etait de 65 ans (35–82). Sept (22 %) d’entre eux presentaient un envahissement ganglionnaire et huit (26 %) des metastases a distance. La majorite des tumeurs (74 %) etaient classees grade 3 ou 4. Dix-huit patients (58 %) presentaient un carcinome a cellules claires, 12 (39 %) un carcinome papillaire et un une tumeur de Bellini. La surexpression d’Aurora A etait associee a l’envahissement ganglionnaire ( p = 0,001). La surexpression d’Aurora B etait associee a la fois a l’envahissement ganglionnaire ( p = 0,002) et au sous-type histologique, Aurora B etant significativement surexprimee dans le carcinome a cellules claires ( p = 0,001). Conclusions Les kinases Aurora A et B etaient significativement surexprimees dans les CCR presentant un envahissement ganglionnaire et pourraient donc avoir une valeur pronostique.

Adult-type rhabdomyosarcoma (RMS) has been classically defined as a pleomorphic sarcoma with desmin expression occurring in adult patients. To reevaluate this entity, we analyzed a series of 57 cases using immunohistochemistry for desmin, myogenin, alpha smooth muscle actin, h-caldesmon, pankeratin AE1/AE3, epithelial membrane antigen (EMA), S100 protein, CD34, MDM2, and CDK4. In this series, there were 36 men and 21 women aged from 22 to 87 years (median: 59). Tumors were mainly located in the lower limbs (27 cases), trunk wall (15 cases), and upper limbs (10 cases). Most tumors were deeply located (51/54) with a size from 1 to 30 cm (median: 8 cm). Cases were classified in 3 histologic categories: spindle cell RMS (25 cases), pleomorphic RMS (16 cases), and mixed type (16 cases). Forty-one tumors were grade 3 and 16 grade 2. Immunohistochemistry showed that every case was positive for desmin and myogenin. Alpha smooth muscle actin was positive in 21%, pankeratin AE1/AE3 in 20%, and CD34 in 13.2%. Treatment modalities and follow-up were available in 46 cases. Median follow-up was 60.9 months. Eight patients developed a local recurrence and 16 a distant metastasis with a 5-year overall survival rate of 52.6% and a 5-year metastasis-free survival of 62.9%. The only predictive factor for metastasis was histologic grade. In conclusion, adult-type RMS is a rare sarcoma occurring mainly in the extremities and trunk wall with 2 main histologic patterns, spindle cell, and pleomorphic patterns, which represent the end of the spectrum of a single entity.

In a retrospective study of sporadic gastric polyps carried out between 1997 and 2007, we analysed the demographic, endoscopic and histological features of 75 patients with polyps. This study revealed 56 hyperplastic polyps (HP), 17 adenomatous lesions (AP) and 2 inflammatory fibroid polyps (IFP). In hyperplastic polyp, the average age was 71 years ± 15 with a sex ratio 1: 1. The gastric antrum was the main site affected by HP, which measured an average 10 mm. In the 56 cases of HP, removal was by endoscopy in 41% and surgery in 5.3% of cases. The average age for patients presenting with AP was 77 years ± 13 years, with a sex ratio 3: 1. The gastric antrum was the main site of involvement and 90% measured more than 10mm. The adenoma was removed by endoscopy in 57% of the cases and by surgery in 21%. The IFP concerned two patients. The polyps were located in the antrum and measured ≥10 mm. They were removed by surgical treatment. Advanced dysplasia was diagnosed in 3.6% of HP and 18% of AP and carcinoma in 12% of AP. None of the IFP presented signs of dysphasia. Intestinal metaplasia was found in 14% of the HP and 19% of the AP, whereas gastric atrophy was found in 19% and 89% of cases respectively. The adenomas were intestinal in 88% of patients and pyloric in 12%. Dysplasia lesions occurred mainly in intestinal AP.

La sclerose tubereuse de Bourneville (S.T.B.) est une maladie genetique rare, congenitale, de transmission autosomique dominante, dont l’incidence est de 1/6 000 a 1/10 000 naissances. Elle fait partie des phacomatoses et se caracterise par une triade de symptomes : adenomes sebaces, retard mental et epilepsie. C’est une affection multi-systemique et polymorphe, pouvant associer des atteintes neurologiques, dermatologiques, cardio-vasculaires, renales, oculaires, pulmonaires, endocriniennes, abdominales et osseuses. Les manifestations bucco-dentaires sont variees : tumeurs fibromateuses gingivales, hyperplasie gingivale, hemangiome, macroglossie, anomalies de l’email dentaire, retards d’eruption, diasteme, palais haut, fentes labiales et/ou palatines, luette bifide. De plus, des atteintes osseuses benignes maxillaires ont ete decrites. Il existe des formes atypiques ou frustres, pour lesquelles le diagnostic n’est pas aise. Le cas de S.T.B. presente, associe des atteintes cutanees caracteristiques de la maladie et une tumeur gingivale fibreuse benigne, et demontre le caractere frustre et non hereditaire de l’affection.

International audience; A 59-years-old man presented with a one-year history of a painless swelling of his second metacarpophalangeal (MCP) joint of his right hand...

International audience; In contrast to long bone osteosarcoma, mandibular osteosarcoma are highly heterogeneous and morphologically overlap with benign tumors, obscuring diagnosis and treatment selection. Molecular characterization is difficult due to the paucity of available specimens of this rare disease. We aimed to characterize the spectrum of mandibular osteosarcoma using immunohistochemistry and molecular techniques (quantitative polymerase chain reaction, sequencing) and compare them with benign fibro-osseous lesions. Forty-nine paraffin-embedded mandible osteosarcoma tissue samples were collected retrospectively and compared with 10 fibrous dysplasia and 15 ossifying fibroma cases. These were analyzed for molecular markers thought to differ between the different diseases and subtypes: MDM2 (murine double-minute type-2) overexpression; GNAS (guanine nucleotide-binding protein/alpha subunit) mutations; and amplification of MDM2 and/or RASAL1 (RAS protein activator like-1). Five fibroblastic high-grade osteosarcoma subtypes showed MDM2 amplification, including two with a microscopic appearance of high-grade osteosarcoma with part low-grade osteosarcoma (differentiated/dedifferentiated osteosarcoma) and MDM2 overexpression. The other three contained a co-amplification of MDM2 and RASAL1, a signature also described for juvenile ossifying fibroma, with no overexpression of MDM2. These were of the giant cell-rich high-grade osteosarcoma, with areas mimicking juvenile ossifying fibroma (ossifying-fibroma-like osteosarcoma). Our results show that some diagnosed high-grade osteosarcoma are differentiated/dedifferentiated osteosarcomas and harbor an overexpression and amplification of MDM2. In addition, juvenile ossifying fibromas can potentially evolve into giant cell-rich high-grade osteosarcomas and are characterized by a RASAL1 amplification (osteosarcoma with juvenile ossifying fibroma-like genotype). Thus, the presence of a RASAL1 amplification in ossifying fibroma may indicate a requirement for closer follow-up and more aggressive management

Adipocytic tumors are the most common mesenchymal neoplasms, liposarcoma accounting for approximately 20% of soft tissue sarcomas. The differential diagnosis between benign and malignant tumors is often problematic and represents a significant proportion of consultation cases. The goal of this article is to review liposarcoma subtypes, the main benign adipocytic neoplasms: lipoblastoma, hibernoma, spindle/pleomorphic cell lipoma, chondroid lipoma, as well as non adipocytic neoplasms with a lipomatous component such as lipomatous solitary fibrous tumor, emphasizing on practical differential diagnosis issues, and immunohistochemical and molecular tools allowing their resolution.

✓ The authors report an unusual case of multicentric pleomorphic xanthoastrocytoma (PXA) in a 36-year-old woman with neurofibromatosis Type 1 (NF1). Both lesions were diagnosed as PXA but demonstrated different neuroimaging features and very different outcomes. Although the occipital lesion was cured surgically, the cerebellar tumor recurred three times and underwent malignant transformation into an anaplastic oligodendroglioma. The authors discuss the causes of PXA and suggest that it could originate from common bipotential precursor cells with two phenotypes.

Multicentric reticulohistiocytosis (RHM) is a rare non Langherhans cell histiocytosis with skin and joint involvment. Nearly all organs can be involved. Association with cancer occurs in about 25% of cases. Association with auto-immune diseases has also been recorded. Microscopic examination shows a histiocytic nodular infiltrate made of giant cells with ground-glass appearance and PAS positive cytoplasm. Immunostaining shows cell positivity for CD68 and negativity for CD1a and S100 protein. No Birbeck granules are found at ultrastructural examination.

We report a case of a kidney and pancreas transplanted patient, hospitalized for septic hip arthritis. The whole diagnostic work-up including synovial and bone biopsies remained negative. After inefficient empirical anti-bacterial antibiotic treatment, femoral head resection was performed and tissue analysis revealed Aspergillus fumigatus hyphae. Treatment with voriconazole along with hip replacement led to complete recovery. However, drug interaction between immunosuppressive and anti-fungal drugs was complicated by cellular acute graft rejection. Aspergillus fumigatus arthritis is an uncommon and serious infection that should be evoked especially in the case of resistance to anti-microbial antibiotics and/or an atypical clinical picture.

International audience; We report herein a patient treated with vemurafenib for a stage IV melanoma who developed an eruption related to eccrine squamous syringometaplasia (ESS). This entity is a well-described side effect of cytostatic therapies used for malignant neoplasia and is clinically characterized by a symmetric cutaneous eruption composed of papules and vesicles preferentially located on fold and intertriginous areas. It is histologically defined by a squamous metaplasia of eccrine ductal epithelium. ESS represents another skin eruption to be added to the list of cutaneous adverse events associated with vemurafenib, a selective BRAF inhibitor used to treat patients with metastatic melanoma harboring the V600E mutation. The discussion focuses on the pathogenesis of ESS secondary to vemurafenib and on alternative diagnoses.

Pathologic diagnosis requires tissue fixation for histologic and immunohistologic analysis, and formalin is routinely used for this. The disadvantage of this fixative is its inability to preserve nucleic acids. Pathologic tumor diagnosis requires extensive molecular analyses, for which formalin fixation may be not adequate. Recently, an alcohol-based fixative (molecular fixative, MF) was described that allows nucleic acid preservation as well as histologic and immunohistologic studies. Moreover, the MF fixation processing system (Xpress) is fast and is well adapted to a routine process. We evaluated RNA and DNA quality within 1 month and after 1 year for 10 breast carcinomas and 20 sarcomas fixed in MF in comparison with the corresponding frozen tumors. The quality of DNA extracted from the MF-fixed tissue was similar to that extracted from the frozen tumors. The quality of RNA extracted from the MF-fixed tissue was lower than that of frozen tumors; nevertheless, a majority of RNA integrity number (RIN) values were greater than 7. Gene expression quantification by real-time polymerase chain reaction gave comparable results between tumors fixed with MF and frozen tumors. Tissue fixation at 4°C with the MF improved the RNA quality measured by the RIN value. However, after storage for 1 year at room temperature, although DNA quality was preserved, RNA extracted from tissues fixed with the MF was degraded. Tissue fixation with the MF is an important improvement for molecular pathologic diagnosis, enabling a combination of routine pathologic diagnoses and current molecular diagnoses if they are carried out near the processing time.

Multicentric reticulohistiocytosis (RHM) is a rare non Langherhans cell histiocytosis with skin and joint involvment. Nearly all organs can be involved. Association with cancer occurs in about 25% of cases. Association with auto-immune diseases has also been recorded. Microscopic examination shows a histiocytic nodular infiltrate made of giant cells with ground-glass appearance and PAS positive cytoplasm. Immunostaining shows cell positivity for CD68 and negativity for CD1a and S100 protein. No Birbeck granules are found at ultrastructural examination.