Ultrasound of the salivary glands is a strong predictor of labial gland biopsy histopathology in patients with sicca symptoms.

BACKGROUND: The international classification criteria for Sjögren's syndrome necessitate the presence of either extractable nuclear antibody or a characteristic focal inflammatory infiltrate in a minor salivary gland. Thus, patients who are extractable nuclear antibody-negative will need to have a labial salivary gland biopsy, which is an invasive procedure associated with morbidity. The aim of this study was to evaluate the viability of ultrasound imaging of the major salivary glands as a predictor of the histology to explore whether ultrasound can help in stratifying Sjögren's patients and reduce the need for biopsy. METHODS: The records of 85 patients suspected of having Sjögren's syndrome and who have had biopsy and ultrasound were analysed retrospectively. The histology and the ultrasound were reported by experts independently. The reporting was impartial as the examiners were blinded to the results of the other investigations and to the diagnosis. RESULTS: Out of the 85 patients, 34 had positive ultrasound, 29 of whom also had positive histology. Fifty-one patients had negative ultrasound, of whom 49 were also negative for histological features of Sjögren's syndrome. The results show that the ultrasound had a positive predictive value of 85% and a striking negative predicative value of 96% of the histology results. The overall concordance between the ultrasound and the histology was 91% (Kappa = 0.826). CONCLUSIONS: Our study shows that potentially the ultrasound has a role in stratifying patients who are extractable nuclear antibody-negative and can help to prioritize the biopsy for those who have sonographic evidence of SS.

Stromal features are predictive of disease mortality in oral cancer patients.

Worldwide, approximately 405 000 cases of oral cancer (OSCC) are diagnosed each year, with a rising incidence in many countries. Despite advances in surgery and radiotherapy, which remain the standard treatment options, the mortality rate has remained largely unchanged for decades, with a 5-year survival rate of around 50%. OSCC is a heterogeneous disease, staged currently using the TNM classification, supplemented with pathological information from the primary tumour and loco-regional lymph nodes. Although patients with advanced disease show reduced survival, there is no single pathological or molecular feature that identifies aggressive, early-stage tumours. We retrospectively analysed 282 OSCC patients for disease mortality, related to clinical, pathological, and molecular features based on our previous functional studies [EGFR, αvß6 integrin, smooth muscle actin (SMA), p53, p16, EP4]. We found that the strongest independent risk factor of early OSCC death was a feature of stroma rather than tumour cells. After adjusting for all factors, high stromal SMA expression, indicating myofibroblast transdifferentiation, produced the highest hazard ratio (3.06, 95% CI 1.65-5.66) and likelihood ratio (3.6; detection rate: false positive rate) of any feature examined, and was strongly associated with mortality, regardless of disease stage. Functional assays showed that OSCC cells can modulate myofibroblast transdifferentiation through αvß6-dependent TGF-ß1 activation and that myofibroblasts promote OSCC invasion. Finally, we developed a prognostic model using Cox regression with backward elimination; only SMA expression, metastasis, cohesion, and age were significant. This model was independently validated on a patient subset (detection rate 70%; false positive rate 20%; ROC analysis 77%, p < 0.001). Our study highlights the limited prognostic value of TNM staging and suggests that an SMA-positive, myofibroblastic stroma is the strongest predictor of OSCC mortality. Whether used independently or as part of a prognostic model, SMA identifies a significant group of patients with aggressive tumours, regardless of disease stage.