PD-L1 expression in recurrent head and neck squamous cell carcinoma.

PURPOSE: To evaluate the Programmed Cell Death Ligand (PD-L1) expression at diagnosis and relapse in patients with head and neck carcinoma (HNSCC) treated with radio(chemo)therapy. METHODS: PD-L1 immunohistochemistry was performed in tumor cells (TC) and immune cells (IC) in 44 patients and scored as 0 = 0%, 1 = < 5%, 2 = 6-49% or 3 = ≥ 50% cells. RESULTS: PD-L1 expression on TC before RT was scored as 0, 1, 2 and 3 in 28, 4, 8 and 4 patients, respectively. In 10 patients, IC did not show any PD-L1 expression; while in 8, 16, and 10 patients, PD-L1 expression was scored 1, 2 and 3, respectively. At relapse, 7/36 patients had a PD-L1 expression positivation in TC, while the opposite was observed in 6 patients. Overall, survival at 2 years was higher in patients with PD-L1 expression (90% versus 62.5%, p = 0.032). CONCLUSION: PD-L1 expression may vary throughout the course of the disease. A re-evaluation of PD-L1 expression on biopsies at the time of recurrence should be recommended.

Impact of expert pathology review in skin adnexal carcinoma diagnosis: Analysis of 2573 patients from the French CARADERM network.

PURPOSE: To prospectively assess the impact of expert pathological review of skin adnexal carcinoma diagnosis in France. METHODS: From 2014 to 2019, 2573 samples from patients with newly diagnosed or suspected skin adnexal carcinomas were reviewed prospectively by expert pathologists through the national CARADERM (CAncers RAres DERMatologiques) network. Changes in diagnosis between referral and expert review were analysed regarding their potential impact on patient care or prognosis. RESULTS: The samples comprised 2205 newly diagnosed adnexal carcinomas, 129 benign adnexal tumours, 136 basal cell carcinomas, 74 squamous cell carcinomas, six cutaneous metastases and 13 other malignancies. There were 930 (42%) sweat gland carcinomas, of which porocarcinoma (261; 11.8%), microcystic adnexal carcinoma (125; 5.7%) and hidradenocarcinoma (109; 4.9%) were the most frequent subtypes; 778 (35%) hair follicle carcinomas, 238 (11%) sebaceous carcinomas and 212 (10%) extramammary Paget diseases/mammary-like anogenital gland adenocarcinomas. A diagnostic change between referral and expert review occurred in 503 (21.3%) patients, significantly higher for cases sent with a provisional diagnosis seeking an expert second opinion (45.7%) than for cases sent with a formal diagnosis (2.8%) (p < .0001). Sweat gland carcinomas were more prone to diagnostic discrepancies than other tumours (p < .0001), including 1.8% of patients with sweat gland carcinoma subtype misclassification with predicted clinical impact. Changes between benign and malignant conditions occurred in 117 samples (5% of patients). CONCLUSION: The study provides a unique description of the distribution of skin adnexal carcinomas and highlights the importance of expert review for these rare cancers. Optimal clinical management was impacted in a significant proportion of patients.

Memory B-cell aggregates in skin biopsy are diagnostic for primary Sjögren's syndrome.

There is a crucial need for reliable diagnostic criteria for SS. Our objective was to evaluate the frequency of xerosis in patients with primary Sjögren's syndrome (SS), and compare histopathology of cutaneous sweat glands and labial salivary glands (LSGs), with respect to their contribution to the diagnosis. Twenty-two patients with primary SS and 22 matched normal volunteers were invited to rate their skin dryness on a visual analog scale. The skin was dryer (58.3 ± 10.1 versus 38.9 ± 7.6, P < 0.01), and xerosis more frequent (9 of 22 versus 2 of 22, P < 0.02) in the patients than in the controls. The axilla skin was chosen for a 6-mm punch biopsy. Lymphocytic infiltration was seen in the skin of 8 of the 12 patients tested. Two of them had normal LSGs. Most interestingly, B cell infiltrates were identified in patients' skin infiltrates, so that their presence might be a clue to the diagnosis of primary SS. These cell aggregates associated memory CD10-/CD20+/CD27+/IgD- B lymphocytes and immature CD20+/CD24 + lymphocytes. These latter findings strongly suggest that skin biopsies warrant inclusion into the routine clinical care of patients suspected of suffering from primary SS.

Testing for BRAF fusions in patients with advanced BRAF/NRAS/KIT wild-type melanomas permits to identify patients who could benefit of anti-MEK targeted therapy.

Beyond targeted therapy for patients with BRAF-mutated melanomas and immunotherapy in patients lacking BRAF mutations, anti-MEK therapy has been proposed in patients with advanced melanomas harbouring BRAF fusions. BRAF fusions diagnosis in patients with advanced melanomas is the subject of the present study. Using BRAF fluorescent in situ hybridisation (FISH), we searched for BRAF fusions in 74 samples of 66 patients with advanced BRAF/NRAS/KIT wild-type melanomas. We identified 2/66 (3%) patients with BRAF fusions in a brain metastasis of one patient and in a lymph node metastasis and in a cutaneous metastasis for the second patient with 90%-95% of tumour nuclei containing isolated 3'-BRAF FISH signals. As a result, we conclude that BRAF FISH in patients with advanced BRAF/NRAS/KIT wild-type melanomas is a valuable and easy-to-perform test to diagnose BRAF fusions and to identify patients who could benefit of anti-MEK targeted therapy.

Dual NRASQ61R and BRAFV600E mutation-specific immunohistochemistry completes molecular screening in melanoma samples in a routine practice.

NRAS and BRAF mutational status has become mandatory to treat patients with metastatic melanomas. Mutation-specific immunohistochemistry (IHC) can help analyze challenging tumor samples. We report our experience integrating NRASQ61R (SP174) and BRAFV600E (VE1) IHC in routine practice in a cancer molecular genetic platform. All samples screened for BRAF and NRAS mutations during the year 2014 were analyzed by IHC and pyrosequencing, with an independent analysis of the 2 methods. Cases with first-line discordant results benefited from a complementary second-round IHC and next-generation sequencing (NGS) with a final interpretation taking into account the results of pyrosequencing, IHC, NGS, and quantification of the tumor cells. We analyzed 111 consecutive formalin-fixed and paraffin-embedded melanoma samples from 101 patients. Twenty-two and 11 samples were concordant for BRAFV600E and NRASQ61R mutations, respectively. Second-round analyses of 9 discordant and 1 molecularly inconclusive samples allowed conclusion in 4 further mutated samples (2 BRAFV600E and 2 NRASQ61R). A sample remained NRASQ61R IHC negative but NRASQ61R mutated with molecular methods. Overall, BRAFV600 and NRASQ61 mutation frequencies were 31.7% and 30.7%, respectively. When compared to molecular results, the sensitivity and specificity of IHC were 100% for BRAFV600E IHC and 92.3% and 98.9% for NRASQ61R IHC, respectively. IHC interpretation required a more stringent cutoff for BRAFV600E IHC than NRASQ61R to minimize false results. We conclude that NRASQ61R and BRAFV600E IHC coupled with NGS allow detection of mutations in melanoma challenging samples.