Is Endoscopic Submucosal Dissection the Option for Early Gastric Cancer Patients with Contraindication to Surgery?

Surgical therapy is the traditional approach for early gastric cancer. Patients with comorbidities cannot benefit from this treatment because of high surgical morbidities and mortalities. Endoscopic submucosal dissection is a new technique for complete en bloc resection of early gastric cancer. We report the case of a patient with severe cardiomyopathy who developed early gastric cancer without metastases present on CT scan. The patient underwent endoscopic submucosal dissection because of the high risk associated to surgery due to severe comorbidity. The patient had complete submucosal dissection with complete en bloc resection. The lateral and deep margins were free of cancerous cells based on histopathology study. The patient was controlled every 6 months for 30 months by endoscopy. Systematic biopsies were done. No recurrences were diagnosed. This report supports the application of endoscopic treatment for patients with early gastric cancer and at high risk for surgery due to comorbidities

Etude de la toxicité hépatique après chimiothérapie systémique pour métastases de cancers colo-recraux

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Lecarcinome hépatocellulaire muté pour le gène de la ß-caténine (une unité morphologique à part)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

Impaired E-cadherin expression and glutamine synthetase overexpression in solid pseudopapillary neoplasm of the pancreas

OBJECTIVES: To analyze in solid pseudopapillary neoplasm of the pancreas (SPNP) the consequences of the deregulated Wnt pathway by studying the expression of Wnt target glutamine synthetase (GLUL), cyclin D1, and E-cadherin, which is one of the beta-catenin binding partner in cell adhesion. METHODS: The expression of cyclin D1 and GLUL was studied at the protein and/or messenger RNA levels, and the immunolocalization for E-cadherin was analyzed in 28 SPNPs screened for beta-catenin mutations. Expression of cyclin D1, GLUL, and beta-catenin was also assessed in pancreatic endocrine tumors as controls. RESULTS: Cytosolic and/or nuclear accumulation of beta-catenin was observed in all tumors; an activating beta-catenin mutation was identified in 21 (91%) of 23 tumors analyzed. E-cadherin expression is lost from the membrane and is observed in intracytosolic "dotlike" structures. Whereas cyclin D1 expression is observed widely in SPNP and endocrine tumors, GLUL expression is restricted to SPNP (100%) and rare endocrine tumors (10%) displaying Wnt activation. CONCLUSIONS: The activation of the Wnt/beta-catenin pathway in SPNP has 2 main consequences. First, E-cadherin expression moved from membranous to intracytoplasmic localization. Second, GLUL expression is highly correlated with Wnt/beta-catenin activation, demonstrating its faithfulness as a Wnt target gene

Occurrence of minimal change nephrotic syndrome in classical Hodgkin lymphoma is closely related to the induction of c-mip in Hodgkin-Reed Sternberg cells and podocytes.

International audienceIt is currently considered that idiopathic minimal change nephrotic syndrome is an immune-mediated glomerular disease. Its association with classical Hodgkin lymphoma minimal change nephrotic syndrome (cHL-MCNS) suggests a molecular link, which remains to be elucidated. We analyzed the expression of cmaf inducing protein (c-mip) in lymphomatous tissues and kidney biopsy samples of patients with cHL-MCNS (n = 8) and in lymphomatous tissues of patients with isolated cHL (n = 9). Because c-mip affects the regulatory loop involving Fyn, we investigated possible structural defects in this signaling pathway, using laser capture microdissection, reverse transcription polymerase chain reaction, and Western blotting. We found that c-mip was selectively expressed in Hodgkin and Reed-Sternberg (HRS) cells and podocytes of patients with cHL-MCNS but is undetectable in patients with isolated cHL. We demonstrated that c-mip was specifically involved in the negative regulation of early proximal signaling through its interaction with phosphoprotein associated with glycosphingolipid-enriched microdomains and Fyn. We showed that the up-regulation of c-mip in cHL-MCNS was associated with a possible Fyn defect in HRS cells and podocytes. Moreover, we showed that c-mip was up-regulated in Fyn-deficient podocytes. c-mip may be a useful marker of cHL-MCNS and its induction reflects the dysregulation of proximal signaling

Biology and Management of High-Grade Chondrosarcoma: An Update on Targets and Treatment Options

This review provides an overview of histopathology, clinical presentation, molecular pathways, and potential new systemic treatments of high-grade chondrosarcomas (CS), including grade 2–3 conventional, dedifferentiated, and mesenchymal CS. The diagnosis of CS combines radiological and histological data in conjunction with patient clinical presentations. Conventional CS is the most frequent subtype of CS (85%) and represents about 25% of primary bone tumors in adults; they can be categorized according to their bone location into central, peripheral, and periosteal chondrosarcomas. Central and peripheral CS differ at the molecular level with either IDH1/2 mutations or EXT1/2 mutations, respectively. CDKN2A/B deletions are also frequent in conventional CS, as well as COL2A1 mutations. Dedifferentiated CS develops when low-grade conventional CS transforms into a high-grade sarcoma and most frequently exhibits features of osteosarcoma, fibrosarcoma, or undifferentiated pleomorphic sarcoma. Their molecular characteristics are similar to conventional CS. Mesenchymal CS is a totally different pathological entity exhibiting recurrent translocations. Their clinical presentation and management are different too. The standard treatment of CSs is wide en-bloc resection. CS are relatively radiotherapy resistant; therefore, doses >60 Gy are needed in an attempt to achieve local control in unresectable tumors. Chemotherapy is possibly effective in mesenchymal chondrosarcoma and is of uncertain value in dedifferentiated chondrosarcoma. Due to resistance to standard anticancer agents, the prognosis is poor in patients with metastatic or unresectable chondrosarcomas. Recently, the refined characterization of the molecular profile, as well as the development of new treatments, allow new therapeutic options for these rare tumors. The efficiency of IDH1 inhibitors in other malignancies suggests that these inhibitors will be part of IDH1/2 mutated conventional CS management soon. Other treatment approaches, such as PIK3-AKT-mTOR inhibitors, cell cycle inhibitors, and epigenetic or immune modulators based on improving our understanding of CS molecular biology, are emerging

c-mip down-regulates NF-κB activity and promotes apoptosis in podocytes.

International audienceThe mechanisms of podocyte disorders in cases of idiopathic nephrotic syndrome (INS) are complex and remain incompletely elucidated. The abnormal regulation of NF-κB may play a key role in the pathophysiology of these podocyte diseases, but at present, NF-κB has not been thoroughly investigated. In this study, we report that induction of c-mip in podocytes of patients with INS is associated with a down-regulation of RelA, a potent antiapoptotic factor that belongs to the NF-κB family. Overexpression of c-mip in differentiated podocytes promotes apoptosis by inducing caspase-3 activity and up-regulating the proapoptotic protein Bax, whereas the overall levels of the antiapoptotic protein Bcl-2 was concomitantly decreased. The associated overexpression of RelA prevented the proapoptotic effects of c-mip. In addition, the targeted induction of c-mip in podocytes in vivo inhibited the expression of the RelA protein and increased the Bax/Bcl-2 ratio. The expression of both c-mip and active caspase-3 increased in focal and segmental glomerulosclerosis biopsies, and both proteins displayed a close spatial relationship. These results suggest that alterations in NF-κB activity might result from the up-regulation of c-mip and are likely to contribute to podocyte disorders in cases of INS

Recurrent novel THBS1-ADGRF5 gene fusion in a new tumor subtype “Acral FibroChondroMyxoid Tumors”

International audienceAcral soft tissue tumors are common neoplasms, a subset of which pose a diagnostic challenge. We report 10 cases of a previously unrecognized acral benign soft tissue tumor. These tumors arose on the fingers and toes and involved bone in half of cases. Histologically, the tumors were lobulated and displayed an abundant stroma made of variable fibrous, chondroid and myxoid material reminiscent of cartilaginous or myoepithelial differentiation. Tumor cells harbored small round to reniform nuclei with clear chromatin and inconspicuous nucleoli along with scant eosinophilic cytoplasm. The cells were mostly arranged haphazardly in the stroma but also in small clusters. No mitotic activity was detected. No specific feature was identified in recurrent cases. By immunohistochemistry, the cells consistently stained for CD34 (10/10), ERG (9/10), and SOX9 (7/10). Whole RNA sequencing identified a previously undescribed recurrent in frame THBS1-ADGRF5 gene fusion in all cases. The transcript was confirmed by RT-PCR and was not found in the control group of mimickers including soft tissue chondromas. We propose the name of Acral FibroChondroMyxoid Tumors for this new entity

Diagnostic histologique des tumeurs osseuses : biopsie chirurgicale ou biopsie percutanée ? Recommandations des pathologistes du réseau de référence des tumeurs osseuses (RESOS)

La prise en charge des patients porteurs d’une lésion osseuse nécessite dans de nombreux cas la réalisation de prélèvements avec analyse anatomopathologique afin d’en déterminer la nature. Avec l’évolution technologique, ces prélèvements sont réalisés de plus en plus souvent de manière ambulatoire et guidés par l’imagerie. L’exiguïté de ces prélèvements peut être à l’origine de difficultés, voire d’erreurs diagnostiques. Les pathologistes du réseau de référence des tumeurs osseuses (RESOS) proposent dans ce document des recommandations concernant le type de prélèvement à réaliser pour le diagnostic anatomopathologique des tumeurs osseuses en fonction des hypothèses diagnostiques formulées à partir des données cliniques et d’imagerie : biopsie chirurgicale ou biopsie radioguidée.[Histological diagnosis of bone tumors: Guidelines of the French committee of bone pathologists reference network on bone tumors (RESOS)]. The management of patients having a bone lesion requires in many cases the realization of a histological sample in order to obtain a diagnosis. However, with the technological evolution, CT-guided biopsies are performed more frequently, often in outpatient clinics. Interpretation of these biopsies constitutes new challenges for the pathologists within the wide spectrum of bone entities. The purpose of the document is to propose guidelines based on the experience of the French committee of bone pathologists of the reference network on bone tumors (RESOS) regarding the indications and limitations of the diagnosis on restricted material