Lymph node excisions provide more precise lymphoma diagnoses than core biopsies: a French Lymphopath network survey.

According to expert guidelines, lymph node surgical excision is the standard of care for lymphoma diagnosis. However, core needle biopsy (CNB) has become widely accepted as part of the lymphoma diagnostic workup over the past decades. The aim of this study was to present the largest multicenter inventory of lymph nodes sampled either by CNB or surgical excision in patients with suspected lymphoma and to compare their diagnostic performance in routine pathologic practice. We reviewed 32 285 cases registered in the French Lymphopath network, which provides a systematic expert review of all lymphoma diagnoses in France, and evaluated the percentage of CNB and surgical excision cases accurately diagnosed according to the World Health Organization classification. Although CNB provided a definitive diagnosis in 92.3% and seemed to be a reliable method of investigation for most patients with suspected lymphoma, it remained less conclusive than surgical excision, which provided a definitive diagnosis in 98.1%. Discordance rates between referral and expert diagnoses were higher on CNB (23.1%) than on surgical excision (21.2%; P = .004), and referral pathologists provided more cases with unclassified lymphoma or equivocal lesion through CNB. In such cases, expert review improved the diagnostic workup by classifying ∼90% of cases, with higher efficacy on surgical excision (93.3%) than CNB (81.4%; P < 10-6). Moreover, diagnostic concordance for reactive lesions was higher on surgical excision than CNB (P = .009). Overall, although CNB accurately diagnoses lymphoma in most instances, it increases the risk of erroneous or nondefinitive conclusions. This large-scale survey also emphasizes the need for systematic expert review in cases of lymphoma suspicion, especially in those sampled by using CNB.

[Staging cancers of the oral cavity according to the 8th edition of AJCC TNM system: Issues and recommendations]. / Tumeurs de la cavité orale et classification TNM (8e édition) : problématiques et recommandations.

Stage of cancer at the time of the diagnosis is a key factor for the prognosis and the determination of appropriate treatment. Several cancer staging systems are used worldwide. The most useful staging system is the tumor, node and metastasis (TNM) staging system develop by the American Joint Committee on Cancer (AJCC) in collaboration with the Union for International Cancer Control (UICC) referred to as the AJCC TNM staging system. The AJCC TNM system classifies cancers by the size and extend of the primary tumor (T), involvement of regional lymph nodes (N) and the presence of distant metastases (M). AJCC and UICC periodically modify the AJCC TNM staging system according to newly acquired clinical, pathological and biological data improving understanding of cancer physiopathology. The 8th edition of AJCC TNM system is effective for cancer patients diagnosed on or after January 1, 2018. Here, we report the issues of the staging cancers of the oral cavity according to the 8th edition of AJCC TNM system. We focus on 2 new concepts defined in the 8th edition of AJCC TNM system: depth of invasion (DOI) and extranodal extension (ENE).

LAIR1, an ITIM-Containing Receptor Involved in Immune Disorders and in Hematological Neoplasms.

Leukocyte-associated immunoglobulin (Ig)-like receptor 1 (LAIR1, CD305) belongs to the family of immune-inhibitory receptors and is widely expressed on hematopoietic mature cells, particularly on immune cells. Four different types of ligands of LAIR1 have been described, including collagens, suggesting a potential immune-regulatory function on the extracellular matrix. By modulating cytokine secretion and cellular functions, LAIR1 displays distinct patterns of expression among NK cell and T/B lymphocyte subsets during their differentiation and cellular activation and plays a major negative immunoregulatory role. Beyond its implications in physiology, the activity of LAIR1 can be inappropriately involved in various autoimmune or inflammatory disorders and has been implicated in cancer physiopathology, including hematological neoplasms. Its action as an inhibitory receptor can result in the dysregulation of immune cellular responses and in immune escape within the tumor microenvironment. Furthermore, when expressed by tumor cells, LAIR1 can modulate their proliferation or invasion properties, with contradictory pro- or anti-tumoral effects depending on tumor type. In this review, we will focus on its role in normal physiological conditions, as well as during pathological situations, including hematological malignancies. We will also discuss potential therapeutic strategies targeting LAIR1 for the treatment of various autoimmune diseases and cancer settings.

BCL2 and BCL6 atypical/unbalanced gene rearrangements in diffuse large B-cell lymphoma are indicators of an aggressive clinical course.

AIMS: Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin's lymphoma that represents a heterogeneous group of disease that is differentially characterised by clinical, molecular and cytogenetic features. MYC, BCL2 and BCL6 gene rearrangements have been identified as prognostic factors in DLBCL, especially for MYC. Nevertheless the frequency and effect of atypical/unbalanced BCL6, BCL2 and MYC translocations in DLBCL is not fully documented. Here, we aimed to analyse those atypical/unbalanced rearrangements in DLBCL and to assess their prognostic impact. METHODS: We collected tumour tissue and clinical data from 97 DLBCL and used interphase fluorescence in situ hybridisation (FISH) with break-apart probe to characterise BCL6, BCL2 and MYC gene pattern. RESULTS: 19 of 97 (19,6%) cases of DLBCL had atypical/ unbalanced gene rearrangements (14 involving BCL6 gene, 5 involving BCL2 gene and none involving MYC gene). Compared with patients with simple gene rearrangement and patients without cytogenetic abnormality, patients with atypical/unbalanced gene rearrangement were in an unfavourable risk group by the International Prognostic Index (p=0039), died of disease (p=0012), harboured relapse or progression (p=0011) and had shorter overall (p=0,04), relapse free (p=0029) and event free (p=0026) survival. CONCLUSIONS: We showed that patients with DLBCL with BCL2 or BCL6 atypical/unbalanced rearrangements constituted a group of patients with poor outcome. We also underlined the importance of FISH analyses, easily feasible in routine practise, at diagnosis of DLBCL to detect the rather frequent and clinically significant atypical/unbalanced aberrations of these genes.

The immune contexture of primary central nervous system diffuse large B cell lymphoma associates with patient survival and specific cell signaling.

Rationale: Primary central nervous system diffuse large B-cell lymphoma (PCNSL) is a rare and aggressive entity that resides in an immune-privileged site. The tumor microenvironment (TME) and the disruption of the immune surveillance influence lymphoma pathogenesis and immunotherapy resistance. Despite growing knowledge on heterogeneous therapeutic responses, no comprehensive description of the PCNSL TME is available. We hence investigated the immune subtypes of PCNSL and their association with molecular signaling and survival. Methods: Analysis of PCNSL transcriptomes (sequencing, n = 20; microarrays, n = 34). Integrated correlation analysis and signaling pathway topology enabled us to infer intercellular interactions. Immunohistopathology and digital imaging were used to validate bioinformatic results. Results: Transcriptomics revealed three immune subtypes: immune-rich, poor, and intermediate. The immune-rich subtype was associated to better survival and characterized by hyper-activation of STAT3 signaling and inflammatory signaling, e.g., IFNγ and TNF-α, resembling the hot subtype described in primary testicular lymphoma and solid cancer. WNT/ß-catenin, HIPPO, and NOTCH signaling were hyper-activated in the immune-poor subtype. HLA down-modulation was clearly associated with a low or intermediate immune infiltration and the absence of T-cell activation. Moreover, HLA class I down-regulation was also correlated with worse survival with implications on immune-intermediate PCNSL that frequently feature reduced HLA expression. A ligand-receptor intercellular network revealed high expression of two immune checkpoints, i.e., CTLA-4/CD86 and TIM-3/LAGLS9. TIM-3 and galectin-9 proteins were clearly upregulated in PCNSL. Conclusion: Altogether, our study reveals that patient stratification according to immune subtypes, HLA status, and immune checkpoint molecule quantification should be considered prior to immune checkpoint inhibitor therapy. Moreover, TIM-3 protein should be considered an axis for future therapeutic development.