EHMT2 affects microglia polarization and aggravates neuronal damage and inflammatory response via regulating HMOX1.

Objective: This research was designed to ascertain the function of euchromatic histone lysine methyltransferase 2 (EHMT2) in ischemic stroke-induced neuronal damage and inflammatory response and its regulatory mechanism. Methods: Mouse microglia (BV-2 cells) were induced by oxygen glucose deprivation/reoxygenation (OGD/R) to establish a cellular model, and then co-cultured with HT22 hippocampal neurons. After that, HT22 cell viability and apoptosis were evaluated, followed by the measurement of apoptosis-related factors (B-cell lymphoma-2, Bcl-2 associated X, and cleaved-Caspase 3). Meanwhile, the expression of inducible nitric oxide synthase (M1 microglia polarization marker) and arginase 1 (M2 microglia polarization marker) in BV-2 cells was detected, as well as the levels of inflammatory factors (tumor necrosis factor-α, interleukin [IL]-6, IL-10, IL-1ß, and IL-4). Additionally, the expression of EHMT2 and heme oxygenase 1 (HMOX1) in BV-2 cells was assessed by quantitative reverse transcription polymerase chain reaction and western blot, and the binding between EHMT2 and HMOX1 was predicted and verified. Results: OGD/R treatment led to decreased cell viability and increased cell apoptosis in HT22 cells, and aggravated inflammatory response in BV-2 cells. In OGD/R-induced BV-2 cells, EHMT2 and HMOX1 were increasingly expressed, and knockdown of EHMT2 or HMOX1 in BV-2 cells could inhibit neuronal damage and inflammatory response. Moreover, EHMT2 promoted HMOX1 transcription level by histone methylation. Conclusion: Collected evidence showed that down-regulation of EHMT2 relieved neuronal damage and inflammatory response by inhibiting HMOX1 expression.

Molecular characterization of sub-frontal recurrent medulloblastomas reveals potential clinical relevance.

Background: Single recurrence in the sub-frontal region after cerebellar medulloblastoma (MB) resection is rare and the underlying molecular characteristics have not been specifically addressed. Methods: We summarized two such cases in our center. All five samples were molecularly profiled for their genome and transcriptome signatures. Results: The recurrent tumors displayed genomic and transcriptomic divergence. Pathway analysis of recurrent tumors showed functional convergence in metabolism, cancer, neuroactive ligand-receptor interaction, and PI3K-AKT signaling pathways. Notably, the sub-frontal recurrent tumors had a much higher proportion (50-86%) of acquired driver mutations than that reported in other recurrent locations. The acquired putative driver genes in the sub-frontal recurrent tumors functionally enriched for chromatin remodeler-associated genes, such as KDM6B, SPEN, CHD4, and CHD7. Furthermore, the germline mutations of our cases showed a significant functional convergence in focal adhesion, cell adhesion molecules, and ECM-receptor interaction. Evolutionary analysis showed that the recurrence could be derived from a single primary tumor lineage or had an intermediate phylogenetic similarity to the matched primary one. Conclusion: Rare single sub-frontal recurrent MBs presented specific mutation signatures that might be related to the under-dose radiation. Particular attention should be paid to optimally covering the sub-frontal cribriform plate during postoperative radiotherapy targeting.

Bone marrow mesenchymal stem cell-derived exosomes carrying long noncoding RNA ZFAS1 alleviate oxidative stress and inflammation in ischemic stroke by inhibiting microRNA-15a-5p.

BACKGROUND/AIM: Bone marrow mesenchymal stem cell (BMSC)-derived exosomes can prevent oxidative stress and inflammation in cerebral ischemia-reperfusion injury. This study intended to assess influences of BMSC-released exosomes on oxidative stress and inflammation following ischemic stroke. METHODS: In vitro and in vivo models were developed using oxygen-glucose deprivation/reperfusion (OGD/R) and middle cerebral artery occlusion (MCAO), respectively. After exosome isolation, co-culture experiments of BMSCs or BMSC-derived exosomes and OGD/R-treated BV-2 cells were implemented to evaluate the impacts of BMSCs or BMSC-secreted exosomes on proliferation, inflammation, oxidative stress, and apoptosis. The gain-of-function experiments of ZFAS1 or microRNA (miR)-15a-5p were conducted to investigate the associated mechanisms. Besides, MCAO mice were injected with exosomes from BMSCs overexpressing ZFAS1 for in vivo verification. The binding of ZFAS1 to miR-15a-5p was assessed through dual-luciferase reporter gene assay. RESULTS: Co-culture with BMSCs accelerated proliferation and downregulated IL-1ß, IL-6, and TNF-α in OGD/R-exposed BV-2 cells, accompanied by increased SOD level and decreased MDA level and apoptosis, all of which were nullified by inhibiting exosome secretion. Mechanistically, ZFAS1 bound to miR-15a-5p to negatively orchestrate its expression. In addition, BMSC-released exosomes or BMSC-secreted exosomal ZFAS1 augmented proliferation but reduced oxidative stress, apoptosis, and inflammation in OGD/R-exposed BV-2 cells, whereas these impacts of BMSC-released exosomal ZFAS1 were nullified by overexpressing miR-15a-5p. Moreover, BMSC-derived exosomal ZFAS1 diminished MCAO-induced oxidative stress, cerebral infarction, and inflammation in mice. CONCLUSIONS: Conclusively, BMSC-released exosomes might carry long noncoding RNA ZFAS1 to curb oxidative stress and inflammation related to ischemic stroke, which was possibly realized through miR-15a-5p inhibition.

Atypical Squamous Cells of Undetermined Significance Cervical Cytology Report Rate and Histologic Follow-up Findings From the Largest College of American Pathologists-Certified Laboratory in China.

CONTEXT.­: Reports for atypical squamous cells of undetermined significance (ASC-US) and histologic findings are rare in China. OBJECTIVE.­: To analyze the correlation findings of ASC-US cytology with high-risk human papillomavirus (hrHPV) test and histopathologic follow-ups. DESIGN.­: ASC-US cases with hrHPV test and histologic follow-ups between 2011 and 2015 were analyzed at a College of American Pathologists-certified laboratory. RESULTS.­: A total of 2 206 588 Papanicolaou (Pap) tests were performed, including 1 513 265 liquid-based cytology preparations (68.58%), and 693 323 conventional Pap tests (31.42%). The overall ASC-US reporting rate was 3.77% (83 199 of 2 206 588), with the highest in women aged 40 to 49 years. Of 18 574 women with ASC-US Pap and HPV testing, the hrHPV positivity rate was 34.98% (6498 of 18 574) with the highest in women younger than 30 years. A total of 6012 women with ASC-US Pap test findings had histologic follow-ups within 6 months; the overall cervical intraepithelial neoplasia 2 and above (CIN2+) detection rate was 7.87% (473 of 6012). One thousand nine hundred nine women with ASC-US Pap and HPV testing had histologic results. CIN2+ lesion was found in 13.98% (124 of 887) of women with ASC-US Pap/HPV-positive test results, significantly higher than 2.84% (29 of 1022) for women with ASC-US Pap/HPV-negative test results. Cervical squamous cell carcinoma was found in 3.95% (35 of 887) of women with ASC-US/HPV-positive test results. CONCLUSIONS.­: This is one of the largest studies to investigate HPV and histologic follow-up findings in women with ASC-US in China. The ASC-US reporting rate, HPV positivity rate, and CIN2+ detection rate were all within the currently recognized benchmark ranges. These findings may contribute to establishing a baseline for better understanding of the status of cervical screening in China.

Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology: A Prospective Blinded Multicenter Study.

Importance: Approximately 20% of fine-needle aspirations (FNA) of thyroid nodules have indeterminate cytology, most frequently Bethesda category III or IV. Diagnostic surgeries can be avoided for these patients if the nodules are reliably diagnosed as benign without surgery. Objective: To determine the diagnostic accuracy of a multigene classifier (GC) test (ThyroSeq v3) for cytologically indeterminate thyroid nodules. Design, Setting, and Participants: Prospective, blinded cohort study conducted at 10 medical centers, with 782 patients with 1013 nodules enrolled. Eligibility criteria were met in 256 patients with 286 nodules; central pathology review was performed on 274 nodules. Interventions: A total of 286 FNA samples from thyroid nodules underwent molecular analysis using the multigene GC (ThyroSeq v3). Main Outcomes and Measures: The primary outcome was diagnostic accuracy of the test for thyroid nodules with Bethesda III and IV cytology. The secondary outcome was prediction of cancer by specific genetic alterations in Bethesda III to V nodules. Results: Of the 286 cytologically indeterminate nodules, 206 (72%) were benign, 69 (24%) malignant, and 11 (4%) noninvasive follicular thyroid neoplasms with papillary-like nuclei (NIFTP). A total of 257 (90%) nodules (154 Bethesda III, 93 Bethesda IV, and 10 Bethesda V) had informative GC analysis, with 61% classified as negative and 39% as positive. In Bethesda III and IV nodules combined, the test demonstrated a 94% (95% CI, 86%-98%) sensitivity and 82% (95% CI, 75%-87%) specificity. With a cancer/NIFTP prevalence of 28%, the negative predictive value (NPV) was 97% (95% CI, 93%-99%) and the positive predictive value (PPV) was 66% (95% CI, 56%-75%). The observed 3% false-negative rate was similar to that of benign cytology, and the missed cancers were all low-risk tumors. Among nodules testing positive, specific groups of genetic alterations had cancer probabilities varying from 59% to 100%. Conclusions and Relevance: In this prospective, blinded, multicenter study, the multigene GC test demonstrated a high sensitivity/NPV and reasonably high specificity/PPV, which may obviate diagnostic surgery in up to 61% of patients with Bethesda III to IV indeterminate nodules, and up to 82% of all benign nodules with indeterminate cytology. Information on specific genetic alterations obtained from FNA may help inform individualized treatment of patients with a positive test result.

Photocatalytic degradation of rhodamine B catalyzed by TiO2 films on a capillary column.

TiO2 films on a capillary column were prepared using tetrabutoxytitanium as a source of TiO2 via the sol-gel method. The film thickness showed a linear increase with tetrabutoxytitanium concentration. The specific surface area of the film was improved by adding polyethylene glycol with different molecular weights. Under optimal conditions, the prepared film had a good mesoporous structure with specific surface area of 47.72 m2 g-1, and showed nearly spherical nanoparticles with a 10 nm diameter and anatase phase. Influences of the thickness, specific surface area, and initial solution concentration on photodegradation of rhodamine B using TiO2 films as a catalyst were investigated. The results showed that the photodegradation efficiency increased with an increasing thickness and specific surface area of TiO2 films. For a rhodamine B solution of 15 mg L-1, the photodegradation efficiency was 98.33% in 30 min under the optimal conditions. The catalysts could be reused up to eight times with almost the same efficiency, indicating a firm immobilization of films on the inner wall of the capillary. Therefore, TiO2 films are promising for the treatment of wastewater.

HPV test results and histological follow-up results of patients with LSIL Cervical Cytology from the Largest CAP-certified laboratory in China.

BACKGROUND: Age-adjusted evaluations have explored the possible utility of (HPV test results in women with LSIL Pap. We investigated HPV test results and histopathologic follow-up results of LSIL patients from China's largest CAP-certified laboratory. METHODS: Patients with LSIL between 2011 and 2015 from the Guangzhou Kingmed Diagnostics were retrospectively retrieved and their hrHPV test results and histological follow-up results were collected and analyzed. RESULTS: LSIL result was identified in 37,895 cases from 2,206,588 Pap tests (1.7%) including 1,513,265 liquid-based cytology and 693,323 conventional Pap tests. The average of these women was 38.4 years (15-88). The LSIL reporting rate in women <30 years was significantly higher than that in women > 30 years (2.1% vs 1.7%). The age specific reporting LSIL rates declined with increased age. 8,014 of 37,895 (21.2%) women with LSIL cytology also had HC2 HPV test results. 75.8% of women with LSIL Pap tests were hrHPV+ and the HPV+ rates declined with increased age except in patients older than 60 years. Overall histopathologic diagnoses within 6 months after LSIL were identified in 5,987 of 37,895 patients at Guangzhou Kingmed Diagnostics. CIN2/3 was identified in 15.2% patients, CIN1 in 66.9%, negative in 14.9% patients. No invasive carcinoma was found in all patients. Of 8014 patients with LSIL Pap test and HPV testing results, 1727 patients had histological follow-up within 6 months after Pap cytology test and HPV testing. The detection rate of CIN2/3 was significantly higher in patients with positive HPV testing result than that in patients with negative HPV testing result (17.8% vs. 8.1%). Among patients with LSIL/HPV negative tests, CIN2/3 was detected in 1 of 30 (3.3%) women aged 50 years and above, appearing lower than those in women less than 50 years (8.0%, 28/351, P=0.357). CONCLUSION: This is the largest histological follow-up study in women with LSIL Pap from China and the data are helpful in establishing a baseline for better understanding the status of cervical screening in China. The 85.1% positive predict value of LSIL Pap cytology for follow-up CIN lesion was within currently recognized benchmark ranges.

Validation of American Thyroid Association Ultrasound Risk Assessment of Thyroid Nodules Selected for Ultrasound Fine-Needle Aspiration.

OBJECTIVE: The aim of this study was to validate the American Thyroid Association (ATA) sonographic risk assessment of thyroid nodules. METHODS: The ATA sonographic risk assessment was prospectively applied to 206 thyroid nodules selected for ultrasound-guided fine-needle aspiration (US-FNA), and analyzed with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), as well as surgical pathology for the subset undergoing surgical excision. RESULTS: The analysis included 206 thyroid nodules averaging 2.4 cm (range 1-7 cm; standard error of the mean 0.07). Using the ATA US pattern risk assessment, nodules were classified as high (4%), intermediate (31%), low (38%), and very low (26%) risk of malignancy. Nodule size was inversely correlated with sonographic risk assessment, as lower risk nodules were larger on average (p < 0.0001). Malignancy rates determined by cytology/surgical pathology were high 100%, intermediate 11%, low 8%, and very low 2%, which were closely aligned with ATA malignancy risk estimates (high 70-90%, intermediate 10-20%, low 5-10%, and very low 3%). ATA US pattern risk assessment also appropriately predicted the proportion of nodules classified as malignant or suspicious for malignancy through TBSRTC classification-high (77%), intermediate (6%), low (1%), and very low 0%-as well as benign TBSRTC classification-high (0%), intermediate (47%), low (61%), and very low (70%) (p < 0.0001). Malignancy rates of surgically excised, cytologically indeterminate nodules followed ATA sonographic risk stratification (high 100%, intermediate 21%, low 17%, and very low 12%; p = 0.003). CONCLUSION: This prospective study supports the new ATA sonographic pattern risk assessment for selection of thyroid nodules for US-FNA based upon TBSRTC and surgical pathology results. In the setting of indeterminate cytopathology, nodules categorized as atypia of undetermined significance/follicular lesion of undetermined significance with ATA high-risk sonographic patterns have a high likelihood of being malignant.

Thyroid Ultrasound-Guided Fine-Needle Aspiration Cytology Results: Observed Increase in Indeterminate Rate over the Past Decade.

Objectives To evaluate changes in distribution of reported thyroid nodule fine-needle aspiration (FNA) cytopathology results since implementation of the Bethesda classification and revised 2015 American Thyroid Association (ATA) guidelines for selecting nodules for biopsy. Study Design Retrospective review. Setting Tertiary academic medical center. Subjects and Methods Evaluation of ultrasound (US)-guided thyroid FNA by a single surgeon using 2015 ATA nodule selection criteria and Bethesda reporting on 211 thyroid nodules in a 1-year period (2015). Comparison is made to an earlier sample wherein any nodule >1 cm underwent US FNA with cytology reported prior to Bethesda consensus (2006). Results The current cohort involved mostly women (79%); nodules ranged from 1 to 7 cm (mean ± SEM, 2.4 ± 0.07 cm). Mean ± SEM age was 53.5 ± 1.1 years. Bethesda reporting yielded 6% nondiagnostic, 57% benign, 3% malignant, and 34% indeterminate (27% atypia of undetermined significance [AUS]/follicular lesion of undetermined significance [FLUS], 4% follicular neoplasm [FN]/Hürthle neoplasm [HN], and 2% suspicious for malignancy [SFM]). The malignancy rate in indeterminate nodules was 26% (18% AUS/FLUS, 33% FN/HN, and 80% SFM). Age, sex, or nodule size did not correlate with indeterminate cytology. The comparator sample of 447 nodules had significantly different distribution, with 7% nondiagnostic, 80% benign, 5% malignant, and 8% indeterminate ( P < .00001). Conclusion We observed a significantly increased proportion of indeterminate cytology and corresponding decrease in benign nodules compared with an earlier sample, predominately from an increase in AUS/FLUS. Multiple factors are likely involved, including selection of sonographically suspicious nodules for biopsy based upon 2015 ATA guidelines coupled with cytopathological interpretation by a new generation of cytopathologists trained in the era of Bethesda reporting; further study is required to make a definitive conclusion.

Prevalence and Genotype Distribution of HPV Infection in China: Analysis of 51,345 HPV Genotyping Results from China's Largest CAP Certified Laboratory.

INTRODUCTION: The prevalence of cervical Human Papillomavirus (HPV) infection varies greatly worldwide and data regarding HPV prevalence and genotypes in China are limited. METHODS: HPV testing results were retrospectively examined at KingMed Diagnostics, the largest independent pathology laboratory in China, from January 2011 to June 2014. All testing was performed using the 26 HPV Genotyping Panel of Tellgenplex (TM) xMAP™ HPV DNA Test assay (TELLGEN, Shanghai, China). Overall prevalence, age-specific prevalence and genotype distributions were analyzed. RESULTS: A total of 51,345 samples were tested and the overall HPV prevalence was 26%, with 21.12% positive for high risk (HR) HPV and 8.37% positive for low risk HPV. 80% of HPV positive cases were positive for a single HPV type. The three most common HR HPV types detected were HPV-52, -16, and -58, in descending order. HPV-18 was only the 6(th) most common type. When women were divided into three age groups: <30, 30-49, ≥50 years, HR HPV had the highest prevalence rate in women <30 years, and the lowest rate in women 30-49 years of age. The distribution of HR HPV genotypes also varied among these three age groups. CONCLUSIONS: To the best of our knowledge, this is largest routine clinical practice report of HPV prevalence and genotypes in a population of women having limited cervical cancer screening. HPV-52 was the most prevalent HR HPV type in this population of women followed by HPV-16 and HPV-58. The overall and age-specific prevalence and genotype distribution of HR HPV are different in this Chinese population compared to that reported from Western countries.

Prevalence of High-Risk Human Papillomavirus Infection in China: Analysis of 671,163 Human Papillomavirus Test Results From China's Largest College of American Pathologists-Certified Laboratory.

OBJECTIVES: This study on human papillomavirus (HPV) testing in China's largest independent laboratory accredited by the international Laboratory Accreditation Program of the College of American Pathologists extends previous reports on cervical screening test results from this Chinese facility. METHODS: A retrospective laboratory database search from 2007 to 2014 documented high-risk HPV test results using either Hybrid Capture 2 (HC2; Qiagen, Hilden, Germany) or multiplex polymerase chain reaction fluorescence testing (MPFT) methods. RESULTS: During the study period, HPV testing steadily increased, with 643,702 HC2 and 27,641 MPFT HPV tests performed. The mean ages of the tested women were 35.0 years using HC2 and 38.3 years using MPFT. The HC2 HPV-positive rate was 21.7%, significantly higher than 15.7% with MPFT (P < .0001), with bimodal peak incidence in adolescents and women aged 60 to 69 years. CONCLUSIONS: Use of HPV testing in cervical screening is increasing in China. HC2 HPV-positive rates around 20% in all age groups from more than 500,000 tested Chinese women are consistent with previous reports from China and significantly higher than published HC2 HPV-positive rates in populations with more widespread cervical screening. MPFT HPV-positive rates were slightly lower in every age group. The high HPV-positive rate likely reflects limited routine cervical screening and high cervical cancer incidence in China.

Elective central node dissection: Comparison of open to minimally invasive video-assisted approach.

OBJECTIVES/HYPOTHESIS: Compare outcomes of concomitant primary thyroidectomy with elective central neck dissection (CND) by the standard open versus minimally invasive video-assisted (MIVA) approach. STUDY DESIGN: Case series chart review, single institution, tertiary referral center. METHODS: Current Procedural Terminology code 60252 was used to identify patients undergoing CND from February 2005 through June 2012. Therapeutic CND and revision cases were excluded. The MIVA approach was performed in patients with low-risk thyroid carcinoma (cT1 or 2, cN0). Primary outcomes included nodal yield and complications, and secondary outcomes included recurrence. RESULTS: Of 87 eligible patients, 38 were open and 49 were MIVA. The MIVA group was more likely female (88% vs. 68%, P = .03), but groups were similar in age (46.0 vs. 48.6 mean years, P = .37) and percentage of unilateral dissection (69.4% vs. 71.0%, P = .86). The MIVA group was more often pT1 or 2 (86.9% vs. 76.4%, P = .02). Pathological node positivity was 40% overall and not significantly different between groups (43.5% vs. 35.3%, P = .46). Nodal yield was similar between groups (6.4 vs. 6.8, P = .73). Transient recurrent laryngeal nerve paralysis rates were similar (4.1% vs. 2.6%, P = .71). Transient hypoparathyroidism (postanesthesia care unit parathyroid hormone ≤15 pg/mL) was lower in the MIVA group but not statistically significant (29.2% vs. 45.2%, P = .15). No patients experienced permanent hypoparathyroidism or developed clinically detectable structural recurrence. Rates of biochemical response were similar (any thyroglobulin >1 ng/dL) (13.8% vs. 8.0%, P = .86). CONCLUSIONS: Concomitant MIVA thyroidectomy with elective CND appears to be a safe and effective alternative to the open approach for low-risk thyroid carcinoma with similar nodal yield, complications, and recurrence. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1715-1718, 2016.

Prior high-risk HPV testing and Pap test results for 427 invasive cervical cancers in China's largest CAP-certified laboratory.

BACKGROUND: Cervical cancer and its precursor lesions are caused by a persistent high-risk human papillomavirus (hrHPV) infection. hrHPV testing has been reported to have higher sensitivity than Papanicolaou (Pap) testing for the detection of cervical precursor lesions. However, limited data are available for prior human papillomavirus (HPV) testing results for patients later diagnosed with invasive cervical cancer, especially in countries lacking a national cervical cancer screening program such as China. This study investigated prior hrHPV testing results for patients with invasive cervical cancer in China. METHODS: Cases with a histologic diagnosis of invasive cervical carcinoma were retrieved from Guangzhou KingMed Diagnostics (the largest independent pathology laboratory in China); prior hrHPV and Pap test results obtained within the year before the cancer diagnosis were recorded. RESULTS: HPV testing was negative in 7.5% of 427 cases of invasive cervical carcinoma, including squamous cell carcinoma (5%) and adenocarcinoma (25%). In 155 cervical cancer cases with prior hrHPV and Pap testing, the negative rate for Pap testing was 1.9%, and the negative rate for HPV was 9.7%. Furthermore, when only cases of adenocarcinoma (n = 18) were examined, both the hrHPV-negative rate and the Pap-negative rate were higher at 33% and 5.6%, respectively. CONCLUSIONS: These data demonstrate a considerable prior hrHPV-negative rate and a lower prior Pap-negative rate in patients with invasive cervical carcinoma (especially adenocarcinoma) from a population of women without access to an established screening program.

PAX8/PPARγ rearrangement in thyroid nodules predicts follicular-pattern carcinomas, in particular the encapsulated follicular variant of papillary carcinoma.

BACKGROUND: PAX8/PPARγ rearrangement is a common genetic alteration in follicular thyroid carcinoma (FTC) and has been reported with variable frequency in papillary thyroid carcinoma (PTC). The diagnostic and phenotypic features of thyroid nodules positive for PAX8/PPARγ on preoperative examination are not well understood. METHODS: The prevalence of PAX8/PPARγ rearrangement was analyzed in a series of 2015 consecutive thyroid nodules that underwent molecular analysis on cytology specimens and in 446 surgically removed PTCs. For all PAX8/PPARγ positive cases, cytology and surgical pathology slides were examined and the available clinical records were reviewed. RESULTS: Twenty-two PAX8/PPARγ rearrangements were identified, including 16 detected preoperatively and 6 postoperatively. The incidence of PAX8/PPARγ in PTC was 1.1%. Cytologically, most of these nodules were diagnosed as a follicular neoplasm (73%), followed by the diagnosis of atypia of undetermined significance (19%), and none of the cases was diagnosed as cytologically malignant. All nodules with PAX8/PPARγ detected preoperatively and surgical follow-up available were found to be malignant, among which the most common diagnosis was the encapsulated follicular variant of PTC. Overall, among 20 PAX8/PPARγ-positive tumors that were surgically excised, 17 (85%) were PTC and 3 (15%) were FTC. On follow-up available for 17 patients (mean, 22.4 months), 16 PAX8/PPARγ-positive cancers showed no evidence of biochemical or structural recurrence, whereas 1 patient with FTC developed bone metastasis. CONCLUSIONS: In this series, PAX8/PPARγ rearrangement found in thyroid nodules had a 100% predictive value for differentiated thyroid cancer, and was more predictive of PTC than FTC. However, almost all PTC carrying PAX8/PPARγ were encapsulated follicular-pattern tumors, distinguished from FTC only by nuclear features. Although most tumors carrying this mutation appear to be clinically indolent, at least on short-term follow-up, distant metastasis can develop from FTC positive for PAX8/PPARγ.

Clinicopathologic study of serous tubal intraepithelial carcinoma with invasive carcinoma: is serous tubal intraepithelial carcinoma a reliable feature for determining the organ of origin?

In the past several decades, the concept of serous ovarian carcinoma has been revised repeatedly. However, the exact pathogenesis remains controversial. The most popular current concept is origin from the epithelium of the fimbriated ends of the fallopian tubes. The objective of our study was to evaluate the characteristic clinical and morphologic features of serous tubal intraepithelial carcinoma (STIC) and associated invasive carcinomas. One hundred sixteen consecutive cases of STIC seen from 2007 to 2011 were included in this study. High-grade serous carcinoma (HGSC) with or without a mixed component was identified in 107 cases (92.2%), non-HGSC in 5 cases, and STICs without invasive carcinoma in 4 cases. Using conventional criteria, HGSCs were classified as fallopian tube in origin in 65 cases (60.7%), as ovarian in 30 (28.0%), as peritoneal in 9 (8.4%), and as endometrial in 3 (2.8%). Among the 107 cases with HGSCs, most STICs (86; 80%) were present unilaterally, whereas invasive tumors more commonly involved the ovaries bilaterally (79%; 84 cases). These findings support the hypothesis that STIC acts as a precursor lesion for most fallopian tube, ovarian, and peritoneal HGSCs, but not for endometrial HGSC.

Follow-up outcomes of a large cohort of low-risk women with negative imaged liquid-based cytology and negative HPV test results.

Recently updated cervical screening guidelines have proposed a 5-year screening interval for women aged 30 years and older with "double-negative" Papanicolaou (Pap) and high-risk human papillomavirus (hrHPV) results (DNR); however, published US follow-up data on women with DNR tested with US Food and Drug Administration (FDA) - approved HPV testing are limited to studies from Kaiser Permanente using conventional Pap smear cytology. Between July 2005 and June 2006, 4,112 patients with DNR who were screened with computer-imaged liquid-based cytology (LBC) (ThinPrep) and Hybrid Capture 2 (HC2) hrHPV tests of LBC vial fluid were identified. Cytologic or histopathologic data were available for 3,211 patients who were followed up for a mean 44 months. Among 2,960 patients aged 30 years and older with DNR, follow-up cervical abnormalities of cervical intraepithelial neoplasia (CIN) 3 or more severe (CIN3+) were documented in 5 (0.17%), including 1 endocervical adenocarcinoma. After DNR, CIN+ diagnoses were significantly more likely in women younger than 50 years than in older women. These data are consistent with previously published US and international studies that have consistently documented low rates of histopathologic CIN3+ during years of follow-up after DNR. Large-scale nationwide data are needed to further assess the level of risk of invasive cervical cancer after DNR using different available hrHPV testing methods.

Histologic follow-up in patients with Papanicolaou test findings of endometrial cells: results from a large academic women's hospital laboratory.

We studied 1,183 Papanicolaou (Pap) cytology cases (739 with normal endometrial cells [nEMCs], 423 with atypical EMCs [aEMCs], and 21 with endometrial cancer cells [EMCCs] in women 40 years or older) with histologic follow-up. Significant endometrial lesions were found in 2.7%, 18.4%, and 100% of cases with nEMCs, aEMCs, and EMCCs, respectively. Significant lesions were present in women 50 years or older with nEMCs found after day 12 of the menstrual cycle or who were postmenopausal (5.2%), but not in women with nEMCs before day 12 (0.5%) or women younger than 50 years with nEMCs after day 12 (1.6%). Our data indicate that endometrial sampling provides no clinical benefit in women (regardless of age) with nEMCs before day 12 of the menstrual cycle or women younger than 50 years with nEMCs after day 12. Endometrial sampling should be routinely performed in women with aEMCs and in women 50 years or older with nEMCs after day 12 of the menstrual cycle or who are postmenopausal.