Adenosine A2A receptor is a tumor suppressor of NASH-associated hepatocellular carcinoma.

Inhibition of adenosine A2A receptor (A2AR) is a promising approach for cancer immunotherapy currently evaluated in several clinical trials. We here report that anti-obesogenic and anti-inflammatory functions of A2AR, however, significantly restrain hepatocellular carcinoma (HCC) development. Adora2a deletion in mice triggers obesity, non-alcoholic steatohepatitis (NASH), and systemic inflammation, leading to spontaneous HCC and promoting dimethylbenzyl-anthracene (DMBA)- or diethylnitrosamine (DEN)-induced HCC. Conditional Adora2a deletion reveals critical roles of myeloid and hepatocyte-derived A2AR signaling in restraining HCC by limiting hepatic inflammation and steatosis. Remarkably, the impact of A2AR pharmacological blockade on HCC development is dependent on pre-existing NASH. In support of our animal studies, low ADORA2A gene expression in human HCC is associated with cirrhosis, hepatic inflammation, and poor survival. Together, our study uncovers a previously unappreciated tumor-suppressive function for A2AR in the liver and suggests caution in the use of A2AR antagonists in patients with NASH and NASH-associated HCC.

[Impact of digital pathology implementation in Reunion Island]. / Intérêt de la pathologie numérique à La Réunion.

In recent decades, the major scientific advances in oncology have complexified anatomic pathology practice. Collaboration with local and national pathologists is essential for ensuring a high-quality diagnosis. Anatomic pathology is undergoing a digital revolution that implements whole slide imaging in routine pathologic diagnosis. Digital pathology improves diagnostic efficiency, allows remote peer review and consultations (telepathology), and enables the use of artificial intelligence. The implementation of digital pathology is of particular interest in isolated territories, facilitating access to expertise and therefore to specialized diagnosis. This review discusses the impact of digital pathology implementation in French overseas territories, particularly in Reunion Island.

Clinicopathologic and Molecular Study of Hybrid Nerve Sheath Tumors Reveals Their Common Association With Fusions Involving VGLL3.

A subset of benign peripheral nerve sheath tumors are "hybrid" combining several lines of differentiation, most often schwannian and perineurial features. The pathogenesis of these tumors was poorly described until the recent discovery of recurrent VGLL3 rearrangements in hybrid schwannoma/perineuriomas, supporting the hypothesis that this entity represents a distinct subgroup of tumors and not only a morphologic variation of other peripheral nerve sheath tumors. Following this finding, we investigated 10 cases of hybrid peripheral nerve sheath tumors with immunohistochemistry, RNA sequencing, and array comparative genomic hybridization. By light microscopy, 7 tumors were hybrid schwannoma/perineurioma tumors, and 3 were hybrid schwannoma/neurofibroma. Most cases of hybrid schwannoma/perineuriomas displayed VGLL3 rearrangements fused in 5' either to CHD7 or CHD9 (n=6/7) and had simple diploid genetic profiles with few copy number alterations. Compared with a control group composed of 28 tumors associated with varied neural phenotypes, all VGLL3-fused tumors clustered together by transcriptomic analysis. In contrast, 1 case of hybrid schwannoma/perineurioma tumor harbored a CDH9-ZFHX3 fusion, a prominent perineurial component identified by immunohistochemistry and clustered with perineuriomas. No recurrent genetic alteration was seen in the 3 hybrid schwannoma/neurofibromas. To summarize, this study confirms and expands the recent findings on hybrid schwannoma/perineurioma, highlighting the predominance of VGLL3 fusions in these tumors.

Syphilis is a Rare Cause of Erythema Nodosum: A Case Report.

Erythema nodosum (EN) is a dermatological manifestation, the common etiologies of which are already widely described. Here, we report the case of a patient who presented an EN, where the etiology was found to be a rare diagnosis: syphilis, a sexually transmitted infection with various clinical presentations. A 42-year-old female patient without any medical condition presented with a clinical picture associating a maculopapular rash at first, and later on a well-defined hypodermic lesion, clinically suggestive of an EN, on the right forearm. The etiologic workup ruled out sarcoidosis, which was the first suspected diagnosis. Positive VDRL-TPHA and recovery within 15 days after benzathine benzylpenicillin administration allowed the diagnosis of syphilis to be made on the EN. EN is a rare manifestation of syphilis that should be kept in mind in these times of strong recrudescence of the disease among men who have sex with men in mainland France but also among heterosexuals in Reunion Island.

Reliability of tumor-infiltrating lymphocyte and tertiary lymphoid structure assessment in human breast cancer.

The presence of tumor-infiltrating lymphocytes (TIL), reflecting host immune activity, is frequently correlated with better clinical outcomes, particularly in HER2-positive and triple-negative breast cancer. Recent findings suggest that organization of immune infiltrates in tertiary lymphoid structures also has a beneficial effect on survival. This study investigated inter- and intra-observer variation in TIL assessment using conventional hematoxylin-eosin versus immunohistochemical staining to identify immune cells. Global, intratumoral, and stromal TIL, as well as tertiary lymphoid structures were scored independently by experienced pathologists on full-face tumor sections (n=124). The fidelity of scoring infiltrates in core biopsies compared to surgical specimens, and pathological assessment compared to quantitative digital analysis was also evaluated. The inter-observer concordance correlation coefficient was 0.80 for global, 0.72 for intratumoral, and 0.71 for stromal TIL, while the intra-observer concordance correlation coefficient was 0.90 for global, 0.77 for intratumoral, and 0.89 for stromal TIL using immunohistochemical stains. Correlations were lower with hematoxylin-eosin stains, particularly for intratumoral TIL, while global scores had the highest concordance correlation coefficients. Our study concluded that tertiary lymphoid structures are accurately and consistently scored using immunohistochemical but not hematoxylin-eosin stains. A strong association was observed between TIL in core biopsies and surgical samples (R2=0.74) but this did not extend to tertiary lymphoid structures (R2=0.26). TIL scored by pathologists and digital analysis were correlated but our analysis reveals a constant bias between these methods. These data challenge current criteria for TIL and tertiary lymphoid structure assessment in breast cancer and recommend that how pathologists evaluate immune infiltrates be reexamined for future studies.

Incidental pseudolymphomatous bladder inflammatory polyp revealing urinary schistosomiasis.

A 25-year-old female who had returned from a trip to Madagascar that was not reported, underwent an endoscopic bladder polyp resection. Histopathology examination revealed an intense pseudolymphomatous inflammatory polyp caused by a Schistosoma infection. Bladder polyps due to schistosomiasis represent a rare condition in developed countries and have to be ruled out in the case of any intense unexplained inflammation.

[Aero-digestive tract squamous intra-epithelial neoplasia]. / Néoplasie intra-épithéliale épidermoïde des voies aéro-digestives supérieures.

Aero-digestive tract squamous intra-epithelial neoplasia is a disease whose genetic and epigenetic features lead to clinical signs and well codified histologic features. This publication aims to review the molecular alterations which have been identified in these lesions, to clarify the clinical manifestations and to discuss the proposed histological classification.