[Myeloid neoplasms associated with rearrangement of PDGFRB: A rare and tricky disease]. / La néoplasie myéloïde associée à un réarrangement de PDGFRB : une pathologie rare de diagnostic difficile.

In the latest World Health Organization classification (WHO), eosinophilic disorders represent a group of rare pathologic conditions with highly heterogeneous pathophysiology. In this report, we describe a case of myeloid neoplasm associated with eosinophilia and rearrangement of PDGFRB gene in a 67-year-old-male patient hospitalized with cerebellous ataxia. Initial investigations showed a bicytopenia with hypereosinophilia varying from 1.1 to 1.6×109/L. Bone marrow aspiration was rich and showed a heterogeneous distribution of myeloid cells with clusters of promyelocytes and proerythroblasts associated with numerous eosinophils and spindle-shaped mast cells but without excess of blasts, dysplasia nor maturation skewing. These aspects suggested an atypical myeloproliferative neoplasm. Bone marrow biopsy was performed showing also a very high cellularity with area of myeloid and erythroid precursors associated with numerous spindle-shaped mast cells. Diagnoses of unclassified myeloid neoplasm and/or systemic mastocytosis were then proposed. Further chromosome analysis showed a t(5;8) translocation with PDGFRB rearrangement revealed in fluorescent in situ hybridization. Patient was treated with imatinib and intravenous immunoglobulin therapy allowing a significant improvement in neurological symptoms and biological results. Patient condition is currently stable after six lines of treatment. This rare hematopoietic neoplasm displays unusual histological and cytological features and can mimic other myeloproliferative neoplasm. Specific cytogenetics analysis should be considered for such cases with hypereosinophilia to select patients that may benefit from targeted therapy.

High prevalence of unusual KRAS, NRAS, and BRAF mutations in POLE-hypermutated colorectal cancers.

Exonucleasic domain POLE (edPOLE) mutations, which are responsible for a hypermutated tumor phenotype, occur in 1-2% of colorectal cancer (CRC) cases. These alterations represent an emerging biomarker for response to immune checkpoint blockade. This study aimed to assess the molecular characteristics of edPOLE-mutated tumors to facilitate patient screening. Based on opensource data analysis, we compared the prevalence of edPOLE mutations in a control group of unselected CRC patients (n = 222) vs a group enriched for unusual BRAF/RAS mutations (n = 198). Tumor mutational burden (TMB) and immune infiltrate of tumors harboring edPOLE mutations were then analyzed. In total, 420 CRC patients were analyzed: 11 edPOLE-mutated tumors were identified, most frequently in microsatellite (MMR)-proficient young (< 70 years) male patients, with left-sided tumors harboring noncodon 12 KRAS mutation. The prevalence of edPOLE-mutated tumors in the control vs the experimental screening group was, respectively, 0.45% (n = 1) vs 5.0% (n = 10). Among the 11 edPOLE-mutated cases, two had a low TMB, three were hypermutated, and six were ultramutated. EdPOLE-mutated cases had a high CD8+ tumor-infiltrating lymphocyte (TIL) infiltration. These clinicopathological and molecular criteria may help to identify edPOLE mutations associated with a high TMB in CRC, and improve the selection of patients who could benefit from immunotherapy.

Detection of microsatellite instability in a panel of solid tumours with the Idylla MSI Test using extracted DNA.

AIM: During the last few years, determination of microstatellite instability (MSI) status has become a routine part of clinical practice, essentially to detect Lynch syndrome. Recently, MSI testing has increased with the development of immunotherapy and has expanded to a large panel of solid tumours. The aim of our work was to evaluate a fully automated system developed by Biocartis, the Idylla MSI Test, which performs an MSI analysis within 150 min. METHODS: A comparison between pentaplex PCR, immunohistochemistry and Idylla MSI Test was performed in 53 colorectal carcinoma samples, 7 small intestine adenocarcinomas, 15 duodenal and pancreatic adenocarcinomas, 16 gastric tumours, 15 endometrial adenocarcinomas, 5 ovarian carcinomas and 4 cases of urinary tract tumours using extracted DNA. Limit-of-detection (LOD) experiment was also done using a commercial DNA known to harbour MSI phenotype. RESULTS: The overall sensitivity was 94% and the overall specificity was 100%. Two invalid and three false-negative results were observed. Our experiments showed that the amount of DNA loaded into the cartridge was decisive and should be superior to 25 ng. LOD comprised between 4% and 8%. CONCLUSION: Overall, we have demonstrated that the Idylla MSI Test is a rapid and valid option to detect MSI phenotype which can be used in a large panel of solid tumours.

Extrahepatic biliary duplication with heterotopic gastric mucosa in a 46,XX male patient.

Extrahepatic biliary duplication is a rare congenital biliary malformation, even more so when associated with heterotopic gastric mucosa. This case report highlights the difficulty of diagnosing such biliary abnormalities, in particular when the duplicated extrahepatic bile duct is the only structure visible by imaging as it is masking the common bile duct. This report shows that extrahepatic bile duct duplication may be a cause of chronic biliary obstruction and secondary sclerosing cholangitis. It has to be considered as a differential diagnosis of primary sclerosing cholangitis in children and adolescents. Furthermore, a potential link between the 46,XX karyotype and biliary duplication is discussed.

Strongyloides stercoralis disseminated infection in an HIV-infected adult.

In this visual case of Strongyloides stercoralis disseminated infection with Enterobacteriaceae-related invasive infection, we demonstrated the in-host S. stercoralis circulation with DNA found in different fluids and specimens, but also in cerebrospinal fluid (CSF), supporting the role of migrant larvae in the Enterobacteriaceae-related invasive and central nervous system infection.

BK virus-associated collecting duct carcinoma of the renal allograft in a kidney-pancreas allograft recipient.

BK polyomavirus (BKV) nephropathy is a major concern in renal transplantation. Its main consequence is graft loss, which occurs in more than 50% of the cases. De novo renal cell carcinoma in renal allograft is a very rare event. Most of these tumors are papillary or clear cell carcinomas. We report herein the first case of collecting duct carcinoma of the renal allograft in a kidney-pancreas allograft adult recipient. Collecting duct carcinoma occurs long after the cure of a BKV nephropathy. At this time, BKV viremia and viruria were negative as well as the immunostaining for SV40 in the non-tumor kidney. The viral oncoprotein Tag persists only in the tumor cells. To preserve pancreas graft function, we maintained immunosuppression levels. After a 9-months follow-up, the evolution was free from clinical and radiological progression. The oncogenic role of BKV remains controversial in human cancers. However, strong experimental data have shown an association between BKV infection and urologic neoplasms. Further works might precise the exact role of polyomaviruses in renal carcinogenesis. In the meantime, clinical vigilance for early diagnostic of these tumors is mandatory after BKV nephropathy.