Paracoccidioidomycosis (PCM) is the most important systemic mycosis in Latin America. It has been regarded as a multifocal disease, with oral lesions as the prominent feature. To provide useful information concerning the diagnosis and management of the disease, this study describes demographic and clinical data from the medical records of a consecutive series of 66 Brazilian patients from an endemic area, evaluated in a referral centre for oral diagnosis. In this sample of patients, there was a predominance of middle-aged male patients, who were primarily rural workers. Chronic multifocal disease was prevalent, with lesions also detected in the lungs, lymph nodes, skin or adrenal glands. Most of the cases presented with lesions at the gingival mucosa followed by the palate and lips; these conditions occurring in the oral cavity were frequently associated with pain. Importantly, most of the patients sought professional care for oral lesions. The diagnosis was obtained through exfoliative cytology and/or biopsy of the oral lesions. Medical treatment was effective, and there were no mortalities in the sample. The present findings not only confirm the importance of oral lesions in the diagnosis and management of PCM but also illustrate that questions still remain unclear, such as the possibility of direct inoculation of the fungus onto oral tissues.

Phosphatidylinositol-3-kinases are kinases that lead to AKT phosphorylation and thus mTOR and GSK3β activation. These proteins are linked to tumorigenesis, but their roles in driving cervical lymph node (CLN) metastasis of oral squamous cell carcinoma (OSCC) cells are unknown. This study aimed to investigate the role of AKT, mTOR, and GSK3β proteins in the occurrence of CLN metastasis in OSCC patients. Ninety and 18 paraffin-embedded OSCC and oral mucosa samples were included, respectively. We divided our OSCC patients into non-metastasizing (PNM) and metastasizing (PM) groups, and the expression of total AKT, pAKT1, pAKT, GSK3β, pGSK3β, and pmTOR was analyzed by immunohistochemistry. The mean expression of GSK3β, pGSK3β, total AKT, and pmTOR was always higher in the OSCC tissues than that in the controls. A positive correlation was also found among these proteins. Total AKT, pmTOR, and pGSK3β expression was significantly higher in the PNM and PM groups than that in the control group. However, only GSK3β expression was significantly higher in the PM group compared with the PNM group. High expression levels of GSK3β and pGSK3β were significantly associated with CLN metastasis, but only GSK3β remained an independent predictor of CLN metastasis. pGSK3β and CLN metastasis were associated with a poor prognosis, but only the latter remained an independent prognostic parameter. Kaplan-Meier survival curves showed that pGSK3β and CLN metastasis were significantly related to reduced survival rates. These results suggest that AKT and mTOR proteins are involved in OSCC biology and that GSK3β itself may drive CLN metastatic spread of OSCC cells.

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Although NSM is an extremely rare oral tumor, it should be considered in the clinical differential diagnosis of gingival nodules.