An Unusual Case of Recurrent Gingival Epstein-Barr Virus-Positive B-Cell Lymphoproliferation.

Epstein-Barr virus (EBV)-positive mucocutaneous ulceration commonly presents as a B-cell lymphoproliferative process with manifold aspects. There is scarce data on its oral manifestation in the scientific literature. We report the case of a 57-year-old male immunocompromised renal transplant patient who developed recurrent chronic and symptomatic mucosal ulceration facing the mandibular incisor teeth. Pathological examination with microscopic and immunohistochemistry studies revealed a B plasma cell infiltration as well as positive staining for EBV, leading to a diagnosis of EBV-positive mucocutaneous ulceration with B-cell lymphoproliferation after extensive workup. Treatment with rituximab was implemented and led to the healing of the lesion. This lesion develops in geriatric and immunodeficient patients and may require oncological therapies. While it is generally associated with an excellent prognosis, it may be indicative of underlying immunosuppression, and hence oral cavity specialists must be aware of this particular entity.

"Plasma cell gingivitis" encompasses multiple entities: a retrospective series of 37 cases.

BACKGROUND: Plasma cell gingivitis is defined as gingival inflammation comprised of plasma cell infiltrates. This diagnostic criterion is non-specific and underlying mechanisms remain unknown. OBJECTIVES: We performed a multidisciplinary clinico-pathological review of cases previously identified as "gingivitis with plasma cell infiltrates", with assessment of putative contributing factors and critical appraisal of the final diagnosis. MATERIALS & METHODS: Cases previously identified as "gingivitis with plasma cell infiltrates" between 2000 and 2020 were included from archives from the GEMUB group, a French multidisciplinary network of physicians with expertise on oral mucosa. RESULTS: Among the 37 included cases, multidisciplinary clinico-pathological review allowed differential diagnosis in seven cases (oral lichen planus n=4, plasma cell granuloma n=1, plasmacytoma n=1, and mucous membrane pemphigoid n=1). The remaining cases were classified as "reactive plasma cell gingivitis" (induced by drugs, trauma/irritation or periodontal disease) (n=18) or "idiopathic plasma cell gingivitis" when no contributing factors were identified (n=12). Clinico-pathological characteristics did not differ significantly between "reactive" and "idiopathic" cases, preventing us from identifying specific features of "idiopathic" plasma cell gingivitis. CONCLUSION: "Plasma cell gingivitis" is a polymorphous, non-specific entity with various aetiologies, of which the diagnosis requires multidisciplinary anatomo-clinical correlation for exclusion of secondary causes of plasma cell infiltration. Although our study was limited by its retrospective design, most cases of "plasma cell gingivitis" appeared to be associated with an underlying cause. We propose a diagnostic algorithm to properly investigate such cases.

Detection of BRAFV600E by digital PCR on fine-needle aspirate enables rapid initiation of dabrafenib and trametinib in unresectable anaplastic thyroid carcinoma.

Introduction: Recently, targeted therapies using BRAFV600E and MEK inhibitors (dabrafenib and trametinib, respectively) have been recommended in BRAF-mutated anaplastic thyroid carcinoma (ATC). Considering the fast development of ATC, droplet digital PCR (ddPCR) performed on fine-needle aspirate (FNA), which is a rapid, reliable, and low-cost method, appears interesting for the detection of BRAFV600E mutation in these patients and allows early initiation of targeted therapies. Results: In our two patients, both presenting extensive cervical masses inaccessible to surgery, ddPCR results were available in less than 24 h. Therefore, dabrafenib and trametinib were started only a few days after first contact. Conclusions: We suggest that ddPCR on FNA be used in non-resectable cervical masses for rapid BRAFV600E mutation detection in the hope that starting targeted therapies early might improve outcomes.

Immunologically active phenotype by gene expression profiling is associated with clinical benefit from PD-1/PD-L1 inhibitors in real-world head and neck and lung cancer patients.

INTRODUCTION: Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours. METHODS: Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours. Validation of the 'HOT' score was done in 40 HNSCC and 992 NSCLC. Stability of the 'HOT' score was tested in paired HNSCC samples from diagnostic biopsies versus surgically resected specimens, untreated versus recurrent samples, and pre-versus post-cetuximab samples in a total of 76 patients. The association between the 'HOT' score with overall survival (OS) and progression-free survival (PFS) was tested in 184 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. RESULTS: A 27-gene expression based 'HOT' score was correlated with: (i) PD-L1 and IDO1 expression, (ii) TCD8 infiltrate and (iii) activation of the IFN-γ pathway. The HOT score concordance when comparing diagnostic biopsies and surgically resected specimens was higher than in untreated samples versus recurrent or pre-versus post-cetuximab samples. In 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors, the HOT score was associated with an improved OS and PFS in multivariate analysis. CONCLUSION: The 'HOT' score is a simple and robust approach to identify real-world patients with HNSCC and NSCLC immunologically active tumours who may benefit from PD-1/PD-L1 inhibitors.

Datasets for gene expression profiles of head and neck squamous cell carcinoma and lung cancer treated or not by PD1/PD-L1 inhibitors.

Identification of tumors harboring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. In this context, we generated targeted gene expression profiles in three and two independent cohorts of patients with HNSCC or NSCLC respectively, treated or not by PD-1/PD-L1 inhibitors. Notably, we generated two datasets including 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. Clinical information, including detailed survival raw data, is available for each patient, allowing to test association between gene expression data and patient survival (overall and progression-free survival). Moreover, we also generated gene expression datasets of 27 paired HNSCC samples from diagnostic biopsies and versus surgically resected specimens as well as 33 paired HNSCC samples at initial diagnosis (untreated) and at recurrence. Those datasets may allow to test the stability of a given biomarker across paired samples.

Association between sex and survival in patients with head and neck spindle cell carcinoma.

BACKGROUND: Head and neck spindle cell carcinoma (HNSpCC) is a rare histological variant associated with worse outcomes. Our objective was to identify clinicopathological factors associated with survival in patients with HNSpCC compared to patients with conventional head and neck squamous cell carcinoma (HNSCC). METHODS: Using clinical data from the Surveillance, Epidemiology, and End Results database, we performed a survival analysis in patients with HNSpCC or HNSCC between 2004 and 2016. RESULTS: A total of 458 HNSpCC and 77 104 HNSCC were identified, including 17% and 16% female, respectively. Five-year disease-specific survival (DSS) was 63.90% and 73.90% in patients with HNSpCC and HNSCC, respectively. Sex (hazard ratio [HR] for females = 2.816; CI: 1.139-6.965; p = 0.025) was significantly associated with DSS in HNSpCC while no association was observed between sex and DSS in HNSCC. CONCLUSION: HNSpCC in women is a specific subgroup of HNSCC, which is associated with a poor prognosis.

Glut-1 intensity and pattern of expression in thymic epithelial tumors are predictive of WHO subtypes.

OBJECTIVES: Glucose-transporter-1 (Glut-1) may be a useful marker for differentiating B3 thymomas and thymic carcinomas. Since the literature is limited, we undertook a study to evaluate its diagnostic value in a series of thymic epithelial tumors. MATERIALS AND METHODS: Glut-1 expression was studied by the group of pathologists linked to the French national oncological network RYTHMIC. Immunostaining was performed on a whole section of one paraffin block in a series of 92 successive surgical specimens. Patterns (focal, zonal, diffuse) and intensity of Glut-1 expression were assessed and compared with WHO histological subtypes. RESULTS: Expression was mainly restricted to epithelial cells. Immature T-lymphocytes were negative. A diffuse, moderate or strong staining was observed in most thymic carcinomas (15/16). In B3 thymomas (10/11) and in B3 thymomas borderline to thymic carcinomas (5/6), a moderate to strong zonal staining was observed at distance from vessels and fibrous septa. This pattern sometimes created the aspect of an anastomosing network in large cellular lobules. In B1 thymomas, immunostaining highlighted foci of medullary differentiation (7/8). B2 thymomas (n=25) were heterogeneous, with a spectrum of patterns ranging between those of B1 and B3 thymomas. Type A thymomas (n=5) mostly presented a weak positivity but one aggressive case showed zonal moderate/strong positivity. Most AB thymomas (15/17) showed weak to moderate immunostaining in spindle cell areas. In micronodular thymomas (n=3), epithelial cells and B-lymphocytes were weakly positive while follicular dendritic cells were strongly highlighted. One metaplastic thymoma displayed diffuse and moderate positivity. CONCLUSION: Glut-1 expression globally depended on histological subtypes and the staining patterns (diffuse or zonal) were different between thymic carcinomas and type B3 thymomas. A comparative study of Glut-1 expression in atypical versus conventional type A thymomas appears warranted. Otherwise, restriction to epithelial cells makes likely a correlation with clinical assessment of glucose uptake in lymphocyte-poor tumors.