[Clinicopathological characteristics of HPV(+) oropharyngeal squamous cell carcinoma].

Objective: To observe the clinicopathologic features of oropharyngeal squamous cell carcinoma associated with human papilloma virus (OPSCC-HPV) and discuss the role and value of different in situ hybridization (ISH) detection methods for HPV in pathologic diagnosis. Methods: Fifteen cases of OPSCC-HPV were collected from Department of Pathology, Beijing Tongren Hospital, Capital Medical University from January 2016 to August 2018. These cases were diagnosed in accordance with the WHO classification of head and neck tumors. The histopathologic features and the clinicopathologic data were retrospectively analyzed. Immunohistochemistry (two-step EnVision method) was done to evaluate the expression of p16, Ki-67 and p53. ISH was used to detect HPV DNA (6/11 and 16/18). RNAscope technology was used to evaluate the presence of HPV mRNAs (16 and 18). Results: The mean age for the 15 patients (8 males, 7 females) was 47 years (range from 30 to 69 years). OPSCC-HPV typically presentedat an advanced clinical stage, six patients had cervical lymphadenopathy (large and cystic), seven had tonsillar swelling, one had tumor at base of tongue, and one had odynophagia. Microscopically the tumors exhibited distinctive non-keratinizing squamous cell carcinoma morphology. Cervical nodal metastases were large and cystic, with thickening of lymph node capsules. OPSCC-HPV raised from crypt epithelium and extended beneath the tonsillar surface epithelial lining as nests and lobules, often with central necrosis. Tumor cells displayed a high N: C ratio, and high mitotic and apoptotic rates. Tumor nests are often embedded within lymphoid stroma, and may be infiltrated by lymphoid cells.Fifteen cases (15/15) were strongly positive for p16; Ki-67 index were 60%-90%; they were focally positive or negative for p53. Ten cases (10/10) were negative for HPV 6/11 DNA, and one case(1/10) was focally positive for HPV16/18 DNA. Eleven cases (11/11) were strongly positive for HPV16 mRNA, one case was focally positive for HPV18 mRNA. Conclusions: OPSCC-HPV is a pathologically and clinically distinct form of head and neck squamous cell carcinoma. OPSCC-HPV is associated with high-risk HPV (type 16) in all cases. Detection of high-risk HPV16 mRNA by RNAscope is of great significance in the final diagnosis and pathogen identification.

[Value of PET/CT in the prognosis of extranodal NK/T cell lymphoma].

Objective: To explore the value of Positron-Emission Tomography/Computed Tomography (PET/CT) in the prognosis of extranodal NK/T cell lymphoma. Methods: The patients of NK/T cell lymphoma diagnosed from January 2007 to July 2016 in Department of Pathology of Beijing Tongren Hospital were enrolled in this study. Seventy-two in-hospital patients were examined on the invasion of adjecent tissue or organ by PET/CT. The PET/CT results were analyzed retrospectively. Kaplan-Meier method was used to analyze the prognostic value of the positive results by PET/CT on overall survival (OS). Results: There were 54 males and 18 females with median age of 44.5 years (13-75 years). According to Ann Arbor staging system, there were 16 cases (22.2%) in stage Ⅰ, 29 cases (40.3%) in stage Ⅱ, 6 cases (8.3%) in stage Ⅲ and 21 cases (29.2%) in stage Ⅳ. According to the IPI scoring system, there were 34 cases (47.2%) in the low risk group (0-1 point), 21 cases (29.2%) in the low-middle risk group (2 points), 16 cases (22.2%) in the middle-high risk group (3 points), and 1 case (1.4%) in the high risk group (4-5 points) . The median follow-up time was 29.2 months (1-118 months). The disease occured in unilateral nasal cavity in 26 cases (36.1%), bilateral nasal cavities in 36 cases (50.0%), nasopharynx, oropharynx and pharynx in 10 cases (13.9%). The tumors of 51 cases involved the surrounding tissue, including nasal wings in 29 cases (40.3%), nasal sinus in 29 cases (40.3%), maxillofacial soft tissue in 18 cases (25.0%), orbital in 12 cases (16.7%), maxilla and skull base in 8 cases (11.1%), eyelid in 6 cases (8.3%), brain tissue in 3 cases (4.2%), eyeball in 2 cases (2.8%). In addition, cervical and inguinal lymphadenopathy were found in 54 cases (75.0%) . Splenomegaly and hepatomegaly were found in 10 cases (13.9%) and 2 cases (2.8%), respectively. Survival analysis showed that the clinical stage and IPI were significantly associated the clinical prognosis (P=0.000, 0.001, respectively). Involvement of the maxillofacial soft tissue, eyelid, orbital, maxilla and skull base and brain tissue were significantly related to reduced the overall survival time (P=0.006, 0.000, 0.024, 0.001 and 0.015, respectively). Involvement of palate or tonsil, the nosewingand nasal sinus did not show significant shorter overall survival (P=0.091, 0.063, and 0.139, respectively). Cox regression multivariate analysis showed maxilla and skull base involvement was independent adverse prognostic factor (P=0.047). Conclusions: The PET/CT examination can accurately detect the extent of adjacent and distant tissues of tumor involvement of NK/T cell lymphoma by showing the tumor structure and metabolic status, thus has important value in the clinical staging and prognosis predication.

[Genotype-phenotype correlations in multiple endocrine neoplasia type 2].

OBJECTIVE: To evaluate the relationship between different RET mutations and the aggressiveness of hereditary medullary thyroid cancer (HMTC) or the presentation of other endocrine disorders in patients with multiple endocrine neoplasia type 2 (MEN2). METHODS: A total of 73 thyroid medullary carcinoma patients from 22 Chinese kindreds who were treated in our center from 2010 to 2015 were enrolled. RET genes in the patients and their relatives were screened. RESULTS: According to the clinical data and 2015 American Thyroid Association (ATA) guidelines, patients were classified into 3 RET mutation risk groups: Modest, 24 cases; High, 48 cases; and Highest, 1 case. Multivariate analysis showed an increased likelihood of MTC stage III or IV at diagnosis with increasing of age and risk. The likelihood increased 11.6% per year of age at surgery (95% confidence interval, 1.040-1.198; P=0.002). The likelihood in patients with high risk was 7.9 times higher than patients with modest risk (95% confidence interval, 1.607-38.717; P=0.003). Aside from one patient with MEN2B, other 72 patients were MEN2A, of them, 28 cases from 7 kindreds with classical MEN2A (codon 634 & 618), 14 cases from 3 kindreds with cutaneous lichen amyloidosis (codon 634), 4 cases from 1 kindred with Hirschsprung's disease (codon 620), and 26 cases from 10 kindreds with familial MTC. CONCLUSION: The aggressiveness of HMTC and the presentation of other endocrine diseases are related to specific RET mutations. For RET mutation carriers, MTC and other endocrine diseases should be diagnosed and treated early based on the RET genotypes.

Effects of inhibiting PI3K-Akt-mTOR pathway on lipid metabolism homeostasis in goose primary hepatocytes.

UNLABELLED: Phosphatidylinositol-3 kinases (PI3K)-Protein kinase B (Akt)-mammalian target of rapamycin (mTOR) pathway plays an important role in the synthesis and secretion of triacylglycerol. However, the mechanism of PI3K-Akt-mTOR pathway in regulating lipid metabolism of goose liver was poorly understood. The purpose of this study was to determine how PI3K-Akt-mTOR pathway regulating lipid metabolic homeostasis in goose hepatocytes. Goose primary hepatocytes were treated with different PI3K-Akt-mTOR signal inhibitors (LY294002, rapamycin and NVP-BEZ235) for 24 h. The results showed that these inhibitors evidently inhibited PI3K-Akt-mTOR downstream signaling. Meanwhile, these PI3K-Akt-mTOR inhibitors reduced intracellular lipid accumulation, decreased the mRNA expression and protein content of genes involved in the de novo fatty acid synthesis, while increased the transcriptional and protein level of key factors involved in fatty acid oxidation and very low density lipoprotein (VLDL) assembly and secretion. CONCLUSION: These findings suggested that the reduction of lipids accumulation induced-by inhibiting PI3K-Akt-mTOR pathway was closely linked to the decrease of lipogenesis, the increase of fatty acids oxidation, and the increase of VLDL assembly and secretion in goose hepatocytes.