Reticular fibre structure in the differential diagnosis of parathyroid neoplasms.

BACKGROUND: To investigate the characteristics of reticular fibre structure (RFS) in parathyroid adenoma (PTA), atypical parathyroid tumour (APT), and parathyroid carcinoma (PTC), and to assess its value as a diagnostic indicator. METHODS: Clinical data and pathological specimens of patients with PTA, APT or PTC were collected. Reticular fibre staining was performed to observe the characteristics of RFS. This study evaluated the incidence of RFS destruction in parathyroid tumours, compared RFS destruction between primary PTC and recurrent and metastatic PTC, and explored the association between RFS destruction and clinicopathological features of APT and primary PTC. RESULTS: Reticular fibre staining was performed in 50 patients with PTA, 25 patients with APT, and 36 patients with PTC. In PTA cases, a delicate RFS was observed. In both the APT and PTC groups, incomplete RFS areas were observed. The incidence of RFS destruction was different among the PTA, APT, and PTC groups (P < 0.001, χ2-test), at 0% (0/50), 44% (11/25), and 86% (31/36), respectively. When differentiating PTC from APT, the sensitivity and specificity of RFS destruction were 81% and 56%, respectively. The incidence of RFS destruction was 73% (8/11) in the primary PTC group and 92% (23/25) in the recurrent and metastatic PTC groups. In both the APT group and primary PTC group, no correlation was found between RFS destruction and clinicopathological features. CONCLUSION: RFS destruction may indicate that parathyroid tumours have unfavourable biological behaviours.Reticular fibre staining may be a valuable tool for improving the diagnostic accuracy in parathyroid tumours.

Efficacy Assessment and Analysis of Related Factors of Ultrasound-Guided Percutaneous Lauromacrogol Injection for Cystic Thyroid Nodules.

OBJECTIVES: This study aimed to investigate the factors influencing the short-term and long-term efficacy of sclerotherapy for cystic thyroid nodules. METHODS: Ninety-nine cystic thyroid nodules that underwent ultrasound-guided fine-needle aspiration biopsy, detection of thyroglobulin in fine needle aspirate (Tg-FNA), and ultrasound-guided percutaneous lauromacrogol injection were retrospectively enrolled from July 2018 to July 2021. All nodules were followed up at 3 and 12 months after the procedure. Factors related to lauromacrogol injection efficacy, including initial volume, vascularity, pathological types, and Tg-FNA level, were analyzed. The nodules were classified as non-effective (VRR <50%) and effective groups (VRR ≥50%) at 3 months to evaluate short-term prognosis, and non-cured (VRR <90%) and cured groups (VRR ≥90%) at 12 months to evaluate long-term prognosis. RESULTS: The volume of cystic thyroid nodules tended to shrink during follow-up. The resolution rate was 79.80% (79/99) at 3 months and 96.91% (94/97) at 12 months. The cure rate was 80.41% (78/97) at 12 months. Independent factors for the long-term prognosis included Tg-FNA level and vascularity (P  < .05). Only Tg-FNA level was an independent factor for the short-term prognosis (P  < .05). The area under the receiver operating characteristic curve for assessing the efficacy at 3 months was 0.79 (95% confidence interval [CI]: 0.65-0.89). With a cutoff value of Tg-FNA 126.92 ng/mL, the specificity was 0.70, and the sensitivity was 0.85. CONCLUSIONS: Ultrasound-guided percutaneous lauromacrogol injection is an effective treatment option for cystic thyroid nodules. It is less effective in viscous or vascular predominantly cystic nodules.

Sputum cell-free DNA for detection of alterations of multiple driver genes in lung adenocarcinoma.

BACKGROUND: Sputum cell-free DNA (cfDNA) has been confirmed to be a valued surrogate sample for detection of EGFR mutations in patients with lung adenocarcinoma (LAC). Whether it is suitable for detection of mutations of multiple driver genes has not been reported. METHODS: A total of 83 patients with LAC were enrolled and their sputum and paired tumor samples were collected. A next-generation sequencing (NGS)-based 10-gene panel was used to test sputum supernatant-derived cfDNA and paired tumor DNA. The sputum sediments were used for cytological evaluation. RESULTS: The total positive rates of hotspot mutations of the 10 driver genes in sputum cfDNA and matched tissue samples were 65.1% and 77.1%, respectively. The overall detection sensitivity of variants in sputum cfDNA was 81.3% (95% confidence interval [CI], 69.2%, 89.5%) and the specificity was 100% (95% CI, 79.1%, 100%). The sensitivities of testing sputum cfDNA from patients with stage IIIB-IV was 87.0% (95% CI, 74.5%, 94.1%); the sensitivities of testing sputum cfDNA from patients with malignant sputum was 92.3% (95% CI, 78.0%, 98.0%); and the sensitivity of testing sputum cfDNA from patients with malignant sputum in stage IIIB-IV were 94.1% (95% CI, 78.9%, 99.0%). CONCLUSIONS: This study demonstrated that sputum cfDNA were successfully used for the detection of multiple driver genes by NGS. Sputum cfDNA could be a valuable surrogate clinical sample for all-in-one test of mutations to guide target therapies, especially for patients with advanced LAC and malignant sputum.

Germ-line mutations in WDR77 predispose to familial papillary thyroid cancer.

The inheritance of predisposition to nonsyndromic familial nonmedullary thyroid cancer (FNMTC) remains unclear. Here, we report six individuals with papillary thyroid cancer (PTC) in two unrelated nonsyndromic FNMTC families. Whole-exome sequencing revealed two germ-line loss-of-function variants occurring within a 28-bp fragment of WDR77, which encodes a core member of a transmethylase complex formed with the protein arginine methyltransferase PRMT5 that is responsible for histone H4 arginine 3 dimethylation (H4R3me2) in frogs and mammals. To date, the association of WDR77 with susceptibility to cancer in humans is unknown. A very rare heterozygous missense mutation (R198H) in WDR77 exon 6 was identified in one family of three affected siblings. A heterozygous splice-site mutation (c.619+1G > C) at the 5' end of intron 6 is present in three affected members from another family. The R198H variant impairs the interaction of WDR77 with PRMT5, and the splice-site mutation causes exon 6 skipping and results in a marked decrease in mutant messenger RNA, accompanied by obviously reduced H4R3me2 levels in mutation carriers. Knockdown of WDR77 results in increased growth of thyroid cancer cells. Whole-transcriptome analysis of WDR77 mutant patient-derived thyroid tissue showed changes in pathways enriched in the processes of cell cycle promotion and apoptosis inhibition. In summary, we report WDR77 mutations predisposing patients to nonsyndromic familial PTC and link germ-line WDR77 variants to human malignant disease.

Sputum cell-free DNA: Valued surrogate sample for the detection of EGFR exon 20 p.T790M mutation in patients with advanced lung adenocarcinoma and acquired resistance to EGFR-TKIs.

BACKGROUND: Sputum cell-free DNA (cfDNA) is a valuable surrogate sample for assessing EGFR-sensitizing mutations in patients with advanced lung adenocarcinoma. Detecting EGFR exon 20 p.T790 M (p.T790 M) is much more challenging due to its limited availability in tumor tissues. Exploring sputum cfDNA as an alternative for liquid-based sample type in detecting p.T790 M requires potential improvement in clinical practice. METHODS: A total of 34 patients with EGFR-sensitive mutation-positive lung adenocarcinoma and acquired resistance to the first generation of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were enrolled. The sputum samples, and paired tumors and/or plasma samples were tested for p.T790 M mutation and concordance of p.T790 M status among the three sample types was analyzed. RESULTS: The overall concordance rate of p.T790 M mutation between sputum cfDNA and tumor tissue samples was 85.7%, with a sensitivity of 66.7% and a specificity of 100%. The sensitivity for detecting p.T790 M in sputum cfDNA was 100%, 66.7%, and 0% in the three sputum groups of malignant, satisfactory but no malignant cells, and unsatisfactory, respectively. The combined results of plasma cfDNA testing and sputum cfDNA testing further increased the sensitivity to 100% for p.T790 M detection in satisfactory but no malignant cells sputum group. CONCLUSION: These findings revealed that cfDNA from malignant or satisfied but no malignant cells sputum is considered suitable for detecting p.T790 M mutation in patients with acquired resistance to first or second-generation EGFR-TKIs. The sputum cytological pathological evaluation-guided sputum cfDNA testing assists in significantly improving the sensitivity of p.T790 M detection, bringing significant value for the maximal application of third-generation EGFR-TKIs in second-line treatment.

Impact of the COVID-19 pandemic on cytology practice: An international survey in the Asia-Pacific region.

BACKGROUND: The purpose of the current study was to examine the impact of coronavirus disease 2019 (COVID-19) on various aspects of cytology practice in the Asia-Pacific region. METHODS: An online questionnaire was distributed to cytopathology laboratories in 24 Asia-Pacific countries to explore the impact of restrictive measures on access to health care, use of general and personal protective equipment (PPE), and changes in cytology workflow and workload from February to April 2020. RESULTS: A total of 167 cytopathology laboratories from 24 countries responded to the survey; the majority reported that restrictive measures that limited the accessibility of health care services had been implemented in their cities and/or countries (80.8%) and their hospitals (83.8%). The respondents noted that COVID-19 had an impact on the cytologic workflow as well as the workload. Approximately one-half of the participants reported the implementation of new biosafety protocols (54.5%) as well as improvements in laboratory facilities (47.3%). Rearrangement or redeployment of the workforce was reported in 53.3% and 34.1% of laboratories, respectively. The majority of the respondents reported a significant reduction (>10%) in caseload associated with both gynecological (82.0%) and nongynecological specimens (78.4%). Most laboratories reported no significant change in the malignancy rates of both gynecological (67.7%) and nongynecological specimens (58.7%) compared with the same period in 2019. CONCLUSIONS: The results of the survey demonstrated that the COVID-19 pandemic resulted in a significant reduction in the number of cytology specimens examined along with the need to implement new biosafety protocols. These findings underscore the need for the worldwide standardization of biosafety protocols and cytology practice.

Sputum Cell-Free DNA: Valued Surrogate Sample for Detection of EGFR Mutation in Patients with Advanced Lung Adenocarcinoma.

Sputum is a common cytologic sample type, but its potential use in EGFR mutation detection in patients with lung cancer is not fully evaluated. This study established an improved sputum cell-free DNA (cfDNA) extraction method study and applied a super-amplification refractory mutation system to detect the EGFR mutation status in sputum cfDNA. The sputum sediments were used for cytology evaluation. The study included 102 lung adenocarcinoma patients; 65 patients (63.7%) were positive for EGFR mutations in tumor samples. EGFR mutation status was positive in 30 patients (29.4%) by sputum cfDNA testing, achieving an overall sensitivity and specificity of 46.2% and 100%, respectively. Comparison of EGFR mutation status in tumor samples revealed that the sensitivity of testing sputum cfDNA in 40 patients with stage I to IIIA versus 62 patients with stage IIIB to IV was 24% (6/25) versus 65.0% (26/40). Through cytology evaluation, the sputum specimens from 62 advanced patients were classified into three categories: 10 were unsatisfactory; 34 were satisfactory but had no malignant cells; and 18 had malignant cells. The sensitivities of these three categories were 0% (0/8), 71.4% (15/21), and 100% (11/11), respectively. These findings revealed that with the improved cfDNA extraction method and sputum cytology evaluation, sputum cfDNA is a valuable surrogate sample type for detecting clinical EGFR mutations in advanced lung adenocarcinoma patients.

[Cytodiagnosis and cytomorphologic analysis of hematolymphoid malignancy in serous effusion: a study of 23 cases].

OBJECTIVE: To evaluate the value of cytomorphologic and immunocytochemical approaches in the diagnosis of hematologic neoplasms in serous effusion. METHODS: The cytospin and Thinprep smears of effusion specimens were prepared from 23 cases of lymphoid malignancies with histological confirmation and 30 cases of benign effusions used as control. Morphological assessment of the cellular components was conducted, including the ratio of mesothelium to lymphocyte, karyomorphism of lymphoid cell and the presence of apoptosis and mitosis. Immunocytochemical study was performed in all the cases, with flow cytometry in one case. RESULTS: Among the 23 tumor cases, 14 represented disease relapse, and in the remaining nine cases, the serous effusion was the primary manifestation. The proportion of mesothelium was low in the tumor group, being less than 10% in 20 cases (87.0%, 20/23). It was more than 10% in most of benign cases (20/30, 66.7%). Lymphoid cells were prominent (> 80% cells) in 69.6% of the tumor cases, and the cellular component in some control cases (63.3%, 19/30) showed fewer lymphocytes. Nipple-like projection of lymphocytic nuclei could be detected in almost all the tumor cases (91.3%, 21/23), but was occasionally found in the control group (26.7%, 8/30). Apoptosis and mitosis were obvious in lymphomatous effusion, but observed in only 6.7% of the control cases. Significant difference of the previously mentioned cytomorphologic features existed between the tumor and control groups (P < 0.01). The results of immunocytochemical staining in cell block were identical to the corresponding immunohistochemistry, and one case of mantle cell lymphoma was confirmed by flow cytometry. The cytologic findings seen in all the 23 studied cases were in agreement with the corresponding histologic diagnosis. CONCLUSIONS: Some cytomorphologic features, including decreased number of mesothelium, increased number of lymphoid cells, nuclear nipple-like projection, and the presence of apoptosis and mitosis, are very useful for diagnosing lymphoid malignancy in serous effusion. Immunocytochemistry is an important approach to the cytodiagnosis and classification of lymphoma.

[Expression of cytokine IL-1α and S100ß in different types of plaques in Alzheimer's disease].

OBJECTIVE: To study the significance of cytokine IL-1α and S100ß expression in formation and evolution of different types of plaques in Alzheimer's disease. METHODS: Thirty-four autopsy cases of Alzheimer's disease encountered during the period from 1982 to 2008 were retrieved from the archival files of Department of Pathology, Beijing Hospital. Tissue blocks were taken from hippocampus for dual immunostaining for IL-1α/Aß and S100ß/Aß. RESULTS: Immunohistochemical studied for IL-1α/Aß and S100ß/Aß delineated four different types of senile plaques: diffuse non-neuritic plaques, diffuse neuritic plaques, dense-core neuritic plaques and dense-core non-neuritic plaques. The numbers of IL-1α-positive microglias and S100ß-positive astrocytes associated with diffuse neuritic plaques were (7.29 ± 3.04) per mm(2) and (6.49 ± 2.20) per mm(2), respectively. In contrast, the numbers of IL-1α-positive microglias and S100ß-positive astrocytes associated with diffuse non-neuritic plaques, dense-core neuritic plaques and dense-core non-neuritic plaques were (3.24 ± 1.53) per mm(2) and (4.14 ± 1.77) per mm(2), (2.09 ± 1.37) per mm(2) and (2.25 ± 0.83) per mm(2), and (1.38 ± 0.90) per mm(2) and (0.58 ± 0.36) per mm(2), respectively. The numbers of IL-1α-positive microglias and S100ß-positive astrocytes associated with diffuse neuritic plaques were significantly higher than those of the other three types of plaques (P < 0.05). CONCLUSION: The IL-1α-positive microglias and S100ß-positive astrocytes may be of certain significance in transformation of diffuse non-neuritic plaques to diffuse neuritic plaques in Alzheimer's disease.

Treatment of platinum-resistant recurrent ovarian cancer using a "predictive molecule targeted routine chemotherapy" system.

BACKGROUND: Correct drug selection, the key to successful chemotherapy, is one of the most difficult clinical decisions for the treatment of platinum-resistant recurrent ovarian cancer worldwide. The exact procedures for choosing drugs are undefined, currently relying on clinical trials and personal experience, which often results in disappointing outcomes. Here, we propose a new drug selection method, the "predictive molecule targeted routine chemotherapy", to choose relatively sensitive routine drugs and avoid relatively resistant routine drugs based on the specific predictive molecule expression of the individual tumor tissue. METHODS: From January 2004 to June 2008, 26 cases of platinum-resistant recurrent ovarian cancer were prospectively recruited. Their routine chemotherapy drug choice was based on the expression of 6 predictive molecules (including p53) as determined by immunohistochemistry (the predictive molecule targeted routine chemotherapy group). A further 18 cases of platinum-resistant recurrent ovarian cancer were treated by experience and formed the control group. The response rate and the overall survival were compared between the two groups. RESULTS: The response rate to second-line chemotherapy was 28% in the control group and 77% in the predictive molecule targeted routine chemotherapy group (P = 0.002). The response rate to third-line chemotherapy was 14% in the control group and 33% in the predictive molecule targeted routine chemotherapy group (P = 0.268). The median overall survival of the predictive molecule targeted routine chemotherapy group (88 weeks) was significantly longer than the median overall survival of the control group (56 weeks) (P = 0.0315). CONCLUSION: The predictive molecule targeted routine chemotherapy is a new effective protocol for choosing drugs when treating platinum-resistant recurrent ovarian cancer.

[The predictive factors for the response to platinum/paclitaxel based first-line adjuvant chemotherapy in advanced ovarian cancer].

OBJECTIVE: To investigate the predictive factors for the response to platinum/paclitaxel based first-line adjuvant chemotherapy in advanced ovarian cancer. METHODS: Forty-two patients with advanced ovarian cancer underwent complete resection plus platinum/paclitaxel as first-line adjuvant chemotherapy. The clinical outcomes were observed. Immunohistochemistry was used to detect the expression of p53, a tumor suppressor protein, and P-glycoprotein (Pgp), a multi-drug resistance associated gene product, in the specimens resected from operation. Retrospectively analysis of 42 cases r patients with. To calculate the complete response (CR) rate and early recurrence (ER) rate and to observe. The relationship between the parameters about clinical outcomes and some clinico-pathological variables, such as age, pathological type, differentiation degree, residual tumor, and molecular markers p53 and Pgp, was analyzed. RESULTS: Twenty-four patients (57%) showed CR and 7 (13%) showed ER. The CR rate of the p53 positive patients was 74%, higher than that of the p53 negative patients (44%, P = 0.065). The ER rate of the patients with residual tumor less than 2 cm was 4%, significantly lower than those with residual tumor > or = 2 cm (P = 0.018). Logistic regression analysis indicated that Pgp positivity and residual tumor > or = 2 cm were independent risk factors of ER. CONCLUSION: Residual tumor, p53, and Pgp expression are predictive factors for the response to platinum/paclitaxel first-line adjuvant chemotherapy in advanced ovarian cancer. The p53 positive patients are more sensitive to this protocol, and the Pgp positive patients and the patients with residual tumor > or = 2 cm are more resistant to this protocol.

[Predictive value of P53 expression in selecting first-line chemotherapy regimen for advanced epithelial ovarian carcinoma].

BACKGROUND & OBJECTIVE: The first-line adjuvant chemotherapy regimens of ovarian cancer mainly include TC (paclitaxel combined with carboplatin) and PC (cisplatin combined with cyclophosphamide) protocols. This study was to investigate the correlation of P53 expression to treatment outcome of ovarian cancer patients received the above 2 protocols, and explore the predictive value of P53 expression in selecting chemotherapy regimen. METHODS: Records of 53 patients with advanced epithelial ovarian cancer (stage IIIc), treated with TC or PC regimen, were analyzed retrospectively. The expression of P53 was detected by immunohistochemistry. The complete response (CR) rate and progression-free survival (PFS) were compared between TC and PC groups according to P53 status. RESULTS: Of the 53 patients, 22 were P53 positive, of which 13 received TC regimen and 9 received PC regimen; the CR rate was slightly higher in TC group than in PC group (76.9% vs. 33.3%, P=0.054), and PFS was significantly longer in TC group than in PC group (102 weeks vs. 43 weeks, P=0.040). In the subgroup of P53-negative patients, TC group had similar CR rate and PFS to PC group. Multivariate analysis showed that the size of residue was an independent prognostic factor. CONCLUSIONS: P53 detection may play a role in selecting first-line chemotherapy for advanced epithelial ovarian cancer patients: TC regimen is preference for P53-positive patients, PC regimen may be a choice for P53-negative patients. These recommendations should be tested in further trails with large samples.

[The effect of the photoelectric detector on the accuracy of the spectrometer].

An optimized photoelectric detector will increase the precision of a spectrometer, thus indicates an important way to develop high performance spectrometer. With an eye to this, a model describing the process that spectrogram is integrated and sampled by photoelectric detector and restored after low-pass filtering is developed. Based on the model, the influence of the characteristic parameters of the detector on the spectral line in the frequency domain is analyzed and the relation between the full width half maximum (FWHM) of the spectra line and the integral interval, sampling space and sensitivity of the detector is deduced. The conclusion indicates that both the integral interval and sampling space should be 1/6 of the FWHM for a spectral line with gaussian profile as a result of compromise between accuracy and feasibility. Moreover, the critical point deciding the right situation for scanner and array detector is given. Other guide line to optimize the photoelectric detector and increase accuracy is suggested also.

[Expression of apolipoprotein E in Alzheimer's disease and its significance].

OBJECTIVE: To study the association between Alzheimer' s disease (AD) and apolipoprotein E (apoE) polymorphism and apoE epsilon4 allele; and to investigate the role of apoE in senile plaque formation. METHODS: During the period from 1982 to 2003, 27 portmortem cases of AD from the archival files of Department of Pathology of Beijing Hospital, diagnosed according to the consortium to establish a registry for Alzheimer's disease (CERAD) criteria, were enrolled into this study. Among the 27 cases studied, there were 23 cases of definite AD and 4 cases of probable AD. Postmortem brain tissues from 67 neurologically unremarkable deceased were used as age-matched controls. Immunohistochemical study for beta-amyloid (Abeta) and Tau protein, as well as immunohistochemical study for Abeta/apoE, were performed in all AD cases using streptavidin-peroxidase (SP) and double immunostaining ( SP/ABC) methods, respectively. Senile plaques and neurofibrillary tangles in the 23 cases of definite AD were further quantified. The apoE genotypes in all cases were analyzed by polymerase chain reaction and restriction fragment length polymorphism technologies. RESULTS: Immunohistochemical study for Abeta distinguished 4 different types of senile plaques: diffuse non-neuritic plaques, diffuse neuritic plaques, dense-core neuritic plaques and dense-core non-neuritic plaques. Double immunohistochemistry for Abeta/apoE showed that some senile plaques were positive for both Abeta and apoE. The expression rates for Abeta and apoE in these 4 different types of senile plaques were 4. 28%, 84. 71%, 8.50% and 2.51%, respectively. The positivity rate for Abeta/apoE in diffuse neuritic plaques were significantly higher than those in other 3 types (P < 0.01). The frequency of occurrence of apoE epsilon4 allele in AD was significantly higher than that in the control group (P < 0.01). The numbers of senile plaques and neurofibrillary tangles in AD cases with apoE epsilon4 allele were also significantly higher than those in AD cases without apoE epsilon4 allele (P < 0.01). CONCLUSIONS: ApoE polymorphism is associated with AD. The presence of apoE epsilon4 allele carries a higher risk for the development of AD. ApoE may also play an important role in the transformation of diffuse non-neuritic plaques to diffuse neuritic plaques.

[Relationship between apoptosis of neurons and microglia activation in Alzheimer's disease].

OBJECTIVE: To assess the relationship between microglia activation and apoptosis of neurons, and the significance of activated microglias in the formation and progression of senile plaques in Alzheimer's disease. METHODS: IL-1alpha and beta-amyloid immunohistochemistry, combined with TUNEL assay were used to assess brain tissue samples from 10 patients with Alzheimer's disease and 4 negative control cases without neurological disease. RESULTS: The number of resting microglias in the brains of Alzheimer's disease patients was similar to that of the control group (P > 0.05), but the number of activated microglias was significant greater in the Alzheimer's disease patients than that of the controls (P < 0.01). The activated microglias displayed altered size and morphology, and was therefore, categorized into three subtypes as primed, enlarged and phagocytic microglias. The numbers of primed, enlarged and phagocytic microglias were 5.4 +/- 0.87, 11.5 +/- 1.25, and 3.4 +/- 0.32 microglia/mm2 and represented 26.6%, 56.65%, and 16.75% of all activated microglias respectively. The number of TUNEL positive apoptotic neurons was significantly greater in Alzheimer patients than that in the control group (P < 0.05). There was a close relationship between the apoptosis of neurons and the activation of microglias (P < 0.01). The activated microglias were differentially distributed among four different plaque types in Alzheimer patients. Many primed (42.3%) and most of the enlarged and phagocytic microglias (56.2% and 70.6%) were present in the diffuse neuritic plaques. CONCLUSIONS: Hyperplasia and activation of microglias are a common phenomena in AD and may play an important role in its pathogenesis. There is a close relationship between the apoptosis of neurons and activation of microglias. The activation of microglias may play a key pathogenic role in senile plaque formation and progression of Alzheimer disease.