Expression of p16Ink4a protein in pleomorphic adenoma and carcinoma ex pleomorphic adenoma proves diversity of tumour biology and predicts clinical course.

AIMS: The aim of the study is to correlate p16Ink4a expression with the clinical courses of pleomorphic adenoma (PA), its malignant transformation (CaexPA) and treatment outcomes. METHODS: Retrospective analysis (1998-2019) of 47 CaexPA, 148 PA and 22 normal salivary gland samples was performed. PAs were divided into two subsets: clinically 'slow' tumours characterised by stable size or slow growth; and 'fast' tumours with rapid growth rate. RESULTS: Positive p16Ink4a expression was found in 68 PA and 23 CaexPA, and borderline expression in 80 and 20, respectively. All 22 (100%) normal salivary gland samples presented with no p16Ink4a expression. Significant difference in p16Ink4a expression was observed between normal tissue, PA and CaexPA (χ2 (4)=172,19; p=0.0001). The PA clinical subgroups were also evaluated separately, revealing additional statistical relations: 'fast' PA and CaexPA differed significantly in p16Ink4a expression (χ2 (2)=8.06; p=0.01781) while 'slow' PA and CaexPA did not (χ2 (2)=3.09; p=0.2129). 3-year, 5-year and 10-year survival among p16Ink4a positive CaexPA patients was 100%, 90.56% and 60.37%, respectively, and in CaexPA patients with borderline p16Ink4a expression was 90.0%, 73.64% and 22.20%, respectively. Statistically significant difference between expression pattern and survival rate was observed (F Cox test - F (16, 24)=2.31; p=0.03075). CONCLUSIONS: Our study confirms no p16Ink4a expression in normal tissue, but reveals differences in expression between 'fast' and 'slow' PA. We suggest that p16Ink4a overexpression is connected to PA proliferation and subsequent malignant transformation to CaexPA. Borderline p16Ink4a staining correlates with worse prognosis of CaexPA.

Salivary Gland Pleomorphic Adenomas Presenting With Extremely Varied Clinical Courses. A Single Institution Case-Control Study.

OBJECTIVE: Pleomorphic adenomas (PAs) with divergent clinical behavior, differing from the vast majority of PAs, were distinguished. "Fast" PAs are characterized by an unexpectedly short medical history and relatively rapid growth. The reference group consisted of "slow" PAs with very stable biology and long-term progression. We divide the PA group as a whole into three subsets: "fast," "normal," and "slow" tumors. Our goal is a multifactorial analysis of the "fast" and "slow" PA subgroups. METHODS: Consecutive surgeries in a tertiary referral center, the Department of Otolaryngology and Laryngological Surgery, Poznan University of Medical Sciences, Poland, were carried out between 2002 and 2011. Out of 1,154 parotid tumors, 636 (55.1%) were PAs. The data were collected prospectively in collaboration with the Polish National Registry of Benign Salivary Gland Tumors. The main outcome measure was the recurrence rate in "fast" and "slow" PA subgroups. All surgical qualifications and surgeries were performed by two experienced surgeons. RESULTS: Slow PAs, compared to fast PAs, presented in older patients (53.25 ± 15.29 versus 47.92 ± 13.44 years). Multifactor logistic regression analysis with recurrence (yes/no) as the outcome variable, fast/slow as the predictor variable and age, gender, margin, FN status as covariates showed that fast PAs were significantly predicting recurrence vs. slow PAs (p = 0.035). Fast PAs were increasing the risk of PAs 10-fold vs. slow PAs, exp ß = 10.20, CI95 [1.66; 197.87]. The variables impacting relapse were recent accelerated growth of the tumor OR = 3.35 (SE = 0.56), p = 0.030, positive margins OR = 7.18 (SE = 0.57), p < 0.001, incomplete or bare capsule OR = 9.91 (SE = 0.53), p = 0.001 and location III OR = 3.12 (SE = 0.53), p = 0.033. In the multivariate model only positive margin was selected as the best predictor of relapse, OR = 5.01 (SE = 0.60), p = 0.007. CONCLUSIONS: The simple clinical aspect of slow or fast PA progression is of great practical importance and can constitute a surrogate of the final histopathological information that is derived from the surgical specimen. The slow or fast nature of the PA to some extent indicates prognostic features such as recurrence risk. This finding requires correlation with histological and molecular features in further stages of research.

IgA nephropathy associated with coeliac disease.

Coeliac disease (CD) is an autoimmune disorder of the small intestine triggered by ingested gluten from barley, rye and wheat. It can be associated with other autoimmune conditions, such as type 1 diabetes, autoimmune thyroiditis and hepatitis, Sjögren's syndrome and IgA nephropathy (IgAN). We describe here a case of a 24-year-old man with the above-mentioned atypical form of coeliac disease for whom the diagnosis started with renal disorder. The diagnosis of nephrotic syndrome was established and the coexistence with CD was also suspected. In fact, immunoglobulin (Ig) A and IgG antibodies against endomysium and against gliadin were detected in serum of the patient and the endoscopic biopsy of the duodenum revealed stage 3B CD. Percutaneous kidney biopsy was also performed. Class I IgAN was diagnosed. Gluten-free diet, ACE inhibitor and oral iron were introduced to the patient. The improvement of clinical and laboratory disorders of CD as well as gradual remission of the nephrotic syndrome were observed. In conclusion, there may be a small group of patients with IgAN coexisting with CD in whom a gluten-free diet seems to be the treatment of choice for the resolution of kidney disease.

The analysis of expression of p16 protein in group of 53 patients treated for sinonasal inverted papilloma.

INTRODUCTION: Sinonasal inverted papilloma constitute relevant therapeutic problem due to destructive character of growth, tendency to recur and the possibility of malignant transformation. Therefore, many attempts to identify risk factors for inverted papilloma occurrence have been undertaken, as well as research to find markers that would allow for the earlier detection of tumors and the application of adequate therapy. A widely known risk factor of inverted papilloma is HPV infection. One of the markers of HPV infection and the ongoing effect of this change (although arousing some controversy) is the expression of the p16 protein. OBJECTIVE: The aim of the study was to analyze the correlation between the expression of p16 as a surrogate of HPV infection in analyzed histopathological material and epidemiological variables, recurrences or malignant transformation. METHODS: The retrospective study includes a group of 53 patients (18 women and 35 men) undergoing treatment for sinonasal inverted papilloma in the period of 2002-2012. The intensity of the p16 protein in histopathological material was scored as: 0 - no expression, 1 - diffuse expression (borderline) and 2 - positive expression; or 0 - no expression/diffuse expression (borderline); 1 - positive expression. The Ethics Committee agreement was obtained (1089/12; 245/13). RESULTS AND CONCLUSION: There was no statistically significant relationship between the expression of p16 and the age of patients, cigarette smoking, tumor location, tumor staging according to the Krouse and Cannady classification, the presence of dysplasia or the occurrence of relapse.

Adverse histopathological findings in glottic cancer with anterior commissure involvement.

Open partial horizontal laryngectomy (OPHL) specimens include cartilage and lymph nodes. Pathological adverse findings (PAF): perichondrium, cartilage, perineural invasion, microvessel spread and prelaryngeal metastases can be detected histologically. We aimed at examining PAF in OPHL specimens and examining the interdependence with oncological outcomes. Prospective analysis of 254 glottis cancers: 87-T2a, 77-T2b and 90-T3 with anterior commissure (AC) involvement treated by OPHL at tertiary referral centre between 2001 and 2008. In 38/254 patients (15 %) PAF were found (16 prelaryngeal metastases, 22 other); more often in stage T2b/T3 versus T2a (p = 0.008). PAF other than prelaryngeal metastases were found more often in T2b than T2a tumours (p = 0.005). Outcomes revealed that out of 36 patients with local recurrence, 19 had PAF. Comparison of 216 patients with no PAF and 16 patients with prelaryngeal metastases revealed, respectively: 7.9 versus 81.3 % local recurrences (p = 0.034), 3.2 versus 68.8 % nodal recurrences (p = 0.011), 90.7 versus 43.8 % of 5-year organ preservation (p = 0.021) and 92.6 versus 75 % 5-year overall survival (p = 0.022). Out of 10 patients with close margins, 1 developed the local recurrence; impact for organ preservation and overall survival was not significant. In 22/254 cases including the cartilage into the operating specimen were therapeutically meaningful; in 16/254 with prelaryngeal metastases, the impact for larynx preservation and overall survival was significant. T2b patients had higher probability of PAF than T2a. PAF significantly influenced higher local recurrence rate. This finding ensures the authors, that OPHL type II is not the "overtreatment" compared to the TLM.