[Practical application of the Paris system for reporting urinary cytology].

Objective: To validate the diagnostic performance of the Paris system for reporting urinary cytology (TPS). Methods: A total of 7 046 urine cytology samples from 3 402 patients collected in the Department of Pathology, Beijing Hospital, China from January 2020 to January 2022 were analyzed. 488 patients had a biopsy or resection specimen during the follow-up period of 6 months. The sensitivity, specificity, risk of malignancy (ROM) and risk of high-grade malignancy (ROHM) of the TPS were evaluated using histological diagnosis as the golden standard. Results: Among the 7 046 samples, high-grade urothelial carcinoma (HGUC) accounted for 5.7% (399/7 046), suspicious for high-grade urothelial carcinoma (SHGUC) for 3.2% (227/7 046), atypical urothelial cells (AUC) for 8.4% (593/7 046), and negative for high-grade urothelial carcinoma (NHGUC) for 72.9% (5 139/7 046) including low-grade urothelial neoplasm (LGUN) for 0.8% (59/7 046) and insufficient samples for 9.8% (688/7 046). 488 patients had a bladder biopsy or resection in the follow-up of six months, including 314 males and 174 females, aged 27 to 92 years (average, 66 years). The ROHM of TPS was 94.7% in HGUC, 83.3% in SHGUC, 41.3% in AUC and 18.8% in NHGUC. The sensitivity and specificity of urine cytology were 70.1% (169/241) and 97.0% (162/167), respectively. The negative predictive value of NHGUC was 69.2% (162/234). Conclusions: The study has shown that TPS classification has high sensitivity and specificity, high ROHM for HGUC and SHGUC, and high negative predictive value for NHGUC. The application of TPS reporting system can better interpret the clinical significance of cytology samples, improve the accuracy of urine cytopathology and ensure continuous diagnostic consistency.

[Scientific, transparent and applicable rankings of Chinese pathological guidelines and consensus published in the medical journals in 2022].

The STAR tool was used to evaluate and analyze the science, transparency, and applicability of Chinese pathology guidelines and consensus published in medical journals in 2022. There were a total of 18 pathology guidelines and consensuses published in 2022, including 1 guideline and 17 consensuses. The results showed that the guideline score was 21.83 points, lower than the overall guideline average (43.4 points). Consensus ratings scored an average of 27.87 points, on par with the overall consensus level (28.3 points). Areas that scored above the overall level were "conflict of interest" and "working groups", while areas that scored below the overall level were "proposals", "funding", "evidence", "consensus approaches" and "accessibility". To sum up, the formulation of pathology guidelines and consensuses in 2022 is not standardized, and the evidence retrieval process, evidence evaluation methods and grading criteria for recommendations on clinical issues are not provided in the formulation process; the process and method for reaching consensus are not provided, the plan is lacking, and registration is not carried out. It is therefore suggested that guidelines/consensus makers in the field of pathology should attach importance to evidence-based medical evidence, strictly follow guideline formulation methods and processes, further improve the scientific, applicable and transparent guidelines/consensuses in the field, and better provide support for clinicians and patients.

[Recent progress in the treatment of intractable sialolithiasis].

Sialolithiasis occurs in approximately 0.45% to 1.20% of the general population. The typical clinical symptom manifests as a painful swelling of the affected glands after a meal or upon salivary stimulation, which extremely affects the life quality of the patients. With the development of sialendoscopy and lithotripsy, most sialoliths can be successfully removed with preservation of the gland. However, sialoliths in the deep hilar-parenchymal submandibular ducts and impacted parotid stones located in the proximal ducts continue to pose great challenges. Our research center for salivary gland diseases (in Peking University School and Hospital of Stomatology) has used sialendoscopy for 17 years and treated >2 000 patients with salivary gland calculi. The success rate was approximately 92% for submandibular gland calculi and 95% for parotid calculi. A variety of minimally invasive surgical techniques have been applied and developed, which add substantial improvements in the treatment of refractory sialolithiasis. Further, the radiographic positioning criteria and treatment strategy are proposed for these intractable stones. Most of the hilar-parenchymal submandibular stones are successfully removed by a transoral approach, including transoral duct slitting and intraductal basket grasping, while a small portion of superficial stones can be removed by a mini-incision in submandibular area. Impacted stones located in the distal third of parotid gland ducts are removed via "peri-ostium incision", which is applied to avoid a cicatricial stenosis from a direct ostium incision. Impacted parotid stones located in the middle and proximal third of the Stensen's duct are removed via a direct mini-incision or a peri-auricular flap. A direct transcutaneous mini-incision is commonly performed under local anesthesia with an imperceptible scar, and is indicated for most of impacted stones located in the middle third, hilum and intraglandular ducts. By contrast, a peri-auricular flap is performed under general anesthesia with relatively larger operational injury of the gland parenchyma, and should be best reserved for deeper intraglandular stones. Laser lithotripsy has been applied in the treatment of sialolithiasis in the past decade, and holmium ∶YAG laser is reported to have the best therapeutic effects. During the past 3 years, our research group has performed laser lithotripsy for a few cases with intractable salivary stones. From our experiences, withdrawal of the endoscopic tip 0.5-1.0 cm away from the extremity of the laser fiber, consistent saline irrigation, and careful monitoring of gland swelling are of vital importance for avoidance of injuries of the ductal wall and the vulnerable endoscope lens during lithotripsy. Larger calculi require multiple treatment procedures. The risk of ductal stenosis can be alleviated by endoscopic dilation. In summary, appropriate use of various endoscopy-assisted lithotomy helps preserve the gland function in most of the patients with refractory sialolithiasis. Further studies are needed in the following aspects: Transcervical removal of intraglandular submandibular stones, intraductal laser lithotripsy of impacted parotid stones and deep submandibular stones, evaluation of long-term postoperative function of the affected gland, et al.

[Differential expression of LLGL2 in prostate ductal adenocarcinoma and acinar adenocarcinoma and its significance].

Objective: To investigate the expression differences of LLGL2 between prostatic ductal adenocarcinoma (PDA) and prostatic acinar adenocarcinoma, and its potential clinical significance. Methods: Eighteen patients diagnosed of PDA or prostatic acinar adenocarcinoma with PDA component by histopathology during January 2015 and December 2019 in the Beijing Hospital, China were retrospectively studied. The transcriptome analysis was conducted using the tissue of PDA and prostatic acinar adenocarcinoma. Differentially expressed genes and the differences in expression profiles were identified. Further, differentially expressed proteins were verified by immunohistochemistry. Results: The tissue from 8 of the 18 patients were used for transcriptome analysis, the results of which were compared with data from public databases. 129 differentially expressed genes were identified. 45 of them were upregulated while 84 were downregulated. The results of gene enrichment analysis and gene oncology (GO) analysis revealed that the differentially expressed genes were mostly enriched in the hypertrophic cardiomyopathy and interleukin-17 related pathways. GPAT2, LLGL2, MAMDC4, PCSK9 and SMIM6 were differentially expressed between PDA and prostatic acinar adenocarcinoma. Moreover, LLGL2 was more likely expressed in the cytoplasm (P=0.04) than the nucleus (P<0.01) in PDA, compared with prostatic acinar adenocarcinoma. Conclusions: The gene expression profiling indicates that PDA are very similar to prostatic acinar adenocarcinoma. Among the differentially expressed proteins screened and verified in this study, the expression of GPAT2, LLGL2, MAMDC4 and PCSK9 is increased in PDA, while that of SMIM6 is reduced in PDA. The expression of LLGL2 shows significantly different patterns between PDA and prostatic acinar carcinoma, and thus may help differentiate PDA from prostatic acinar adenocarcinoma in clinical practice.

[Diagnostic values of nuclear score combined with cyclin D1 immunocytochemistry in indeterminate thyroid follicular nodules in preoperative fine needle aspiration].

Objective: To assess the feasibility of nuclear score combined with cyclin D1 immunocytochemistry in classifying indeterminate thyroid nodules with fine-needle aspiration (FNA) cytological diagnosis of Bethesda category Ⅲ-Ⅴ. Methods: A consecutive cohort of 118 thyroid FNA specimens with indeterminate diagnosis (TBSRTC category Ⅲ-Ⅴ) and available histopathologic follow-up data were collected between December 2018 and April 2022 at the Department of Pathology, Beijing Hospital, China. These cases were subjected to cytological evaluation and cyclin D1 immunocytochemistry. The optimal cut-off points of a simplified nuclear score and the percentage of cyclin D1-positive cells for the diagnosis of malignancy or low-risk neoplasm were determined using the receiver operating characteristic (ROC) curves and area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of nuclear score and cyclin D1 immunostaining were evaluated from the crosstabs based on cut-off points. The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining was estimated using ROC curve analysis. Results: Nuclear grooves, intra-nuclear inclusions and chromatin clearing were more commonly found in malignancy/low-risk neoplasms than benign lesions (P=0.001, P=0.012 and P=0.001 respectively). A cut-off point of≥2 for the simplified nuclear score was sensitive for defining malignancy/low-risk neoplasm, and its PPV, NPV, sensitivity and specificity were 93.6%, 87.5%, 99.0% and 50.0% respectively. A positive cut-off point of 10% positive thyroid cells in cyclin D1 immunostaining demonstrated sensitivity of 88.5%, specificity of 100%, PPV of 100% and NPV of 53.8% for correctly detecting thyroid malignancy or low-risk neoplasm. The sensitivity and PPV of simplified nuclear score combined with cyclin D1 immunostaining were 93.3% and 100%, respectively. Both specificity and NPV were maintained at high levels (100% and 66.7%, respectively). The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining in detecting thyroid malignancy/low-risk neoplasm was increased to 94.1% compared to using either of them alone. Conclusions: Combing simplified nuclear score and cyclin D1 immunostaining on FNA cytology specimens can increase the diagnostic accuracy in classifying thyroid nodules of indeterminate cytological categories. Thus, this supplementary approach provides a simple, accurate, and convenient diagnostic method for cytopathologists so that may reduce unnecessary thyroidectomies.

[Establishment and application of new techniques for submandibular gland preservation].

The saliva secreted from submandibular gland (SMG) accounts for 60%-65%. It plays an important role in maintaining the human function of swallow, digestion, testing, speech, protection of oral mucosa, and prevention from dental carries. The SMG is frequently resected during the treatment for various kinds of oral and maxillofacial diseases, resulting in xerostomia and decreased quality of life. During the past 15 years, Research Center of Salivary Gland Diseases in Peking University School and Hospital of Stomatology conducted a series of studies on new techniques for preservation of SMG and achieved remarkable results. The clinicopathologic and imaging characteristics of IgG4-related sialadenitis (IgG4-RS) were clarified based on systematic studies. The results of studies on the pathogenesis of IgG4-RS showed that unbalance of inflammatory factors mediated the abnormality of secretion of SMG. IL-4 participates in occurring and development of glandular fibrosis of SMG. Regulation of tumor necrosis factor α (TNF-α) and cleaning of senescent cells might be taken as the targets for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents showed effective results for treating IgG4-RS, clinical remission was achieved in all the patients, serum IgG4 levels decreased, and salivary gland secretion significantly increased. Sialoendoscopy-assisted sialolithectomy was applied in the treatment of about 1 000 cases with submandibular hilar calculi with a success rate of more than 90%. Transfer of SMG was used for prevention from radiation-induced xerostomia in the patients with head and neck carcinoma. SMG was transferred to the submental region before radiotherapy and was kept away from the ra-diation field. The results of prospective clinical controlled study showed this technique could effectively preserve the function of SMG and prevent from xerostomia. Based on the micro-anatomical study on the blood vessels and ducts of SMG, partial sialoadenectomy was applied for treatment of benign tumors in the SMG. A clinical controlled study confirmed its safety for control of the tumors and its advantage of preservation of SMG function. The studies on the involvement of SMG in oral squamous cell carcinoma (OSCC) provided the anatomical and histopathological basis for preservation of SMG during neck dissection for early cases with OSCC. A innovated surgical modality "four preservations including SMG" was used during the neck dissection for the early cases with OSCC. A prospective randomized clinical controlled study confirmed its safety, feasibility, effectiveness for control of the carcinoma, and advantages of preservation of SMG function.

[Studies on newly recognized chronic sialadenitis].

Some kinds of chronic sialadenitis were recognized during the recent years. They have specific pathogenesis, clinical and histopathologic appearances, and require specific treatment. IgG4-related sialadenitis (IgG4-RS) is one of the immune-mediated diseases, characterized by tumefactive lesions. The incidence of IgG4-RS obviously increased during the past 30 years. The study on the potential relationship between occupational exposure to chemical substances and the incidence of IgG4-RS showed that subjects with occupational exposure to agents known to cause IgG4-RD had an increased risk for IgG4-RS. Surgical excision of involved SMG could not control the disease progression, which is not recommended for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents is effective for treating IgG4-RS, and restores salivary gland function. Radioiodine induced sialadenitis (RAIS) is one of the common complications of postoperative adjuvant treatment of differentiated thyroid cancer by 131I. The incidence of the disease is related to radiation dosage. Clinically, the patients suffered from swelling and tenderness in the buccal or submandibular regions, especially during the mealtime. Imaging appearances are similar to those of chronic obstructive sialadenitis. Conservative managements, such as gland massage, sialagogues, are the mainstream methods in the treatment of RAIS. Sialendoscopy is feasible for RAIS, but not as effective as conventional obstructive sialadenitis (COS). Therefore the prevention of RAIS is crucial. Eosinophilic sialodochitis (ES) is a new type of chronic inflammatory disease of the salivary gland related to allergy. It has characteristics of swelling of multiple major salivary glands, strip-like gelatinous plugs discharged from the duct orifice of the gland, elevated level of serum IgE and eosinophils in peripheral blood, infiltration of eosinophils and IgE positive plasma cells in the tissues, allergic history, increased expression of allergy-related cytokines, such as IL-4, IL-5, IL-13, and eotaxin, which suggest allergic reactions as a potential pathogenesis of the disease. The clinical, laboratory, histological, and immunohistochemical characteristics of ES are significantly different from conventional obstructive sialadenitis (COS). Therefore, it is suitable to separate ES from COS. Conservative managements, such as self-maintenance therapy and anti- allergic modality are the choices of treatment for ES. Based on the results of our comprehensive studies a new classification of chronic sialadenitis is suggested.

[Clinicopathological significance of 114 cases with positive surgical margin in radical prostatectomy specimens].

Objective: To analyze the clinicopathological features of positive surgical margins (PSM) after radical prostatectomy and to explore its associated factors. Method: A retrospective analysis was conducted on 274 patients who underwent radical prostatectomy in Beijing Hospital from June 2018 to June 2021. The margins of these specimens of radical prostatectomy were directly inked with black ink. According to the margin status (tumor present versus not), the patients were divided into PSM and negative surgical margin (NSM) groups. The clinicopathological characteristics were compared between two groups, including age, preoperative prostate specific antigen (PSA), number of tumors, tumor's location, postoperative pathological Gleason score, tumor burden and postoperative pathological staging. Results: Among the 274 cases, 114 showed PSM, and 160 showed NSM. PSM accounted for 41.6% of the cases. The mean age was 68.3 years, while the PSM group's mean age was 68.0 years, and that of the NSM group was 68.6 years, with no statistical significance between groups (P>0.05). The mean preoperative PSA was 15.8 µg/L in all patients, 21.5 µg/L in the PSM group and 11.3 µg/L in NSM group. PSA in the PSM group was statistically higher than that in the NSM group (P<0.001). The PSA level (10 µg/L, 10-20 µg/L, and >20 µg/L) was associated with the PSM rate (31.1%, 48.7%, and 69.4%). Regarding tumor numbers, 118 cases had a single focus, including 40 cases with PSM (33.9%). In the 156 cases of multiple foci, 74 cases had a PSM (47.4%). There were statistically more PSM cases in the cases with multi-focal disease (P<0.05). Tumors were seen in the transit zone of 44 cases, while 107 cases showed tumors in the peripheral zone, and 123 cases in the whole zone. The PSM rate was 27.3% (12/44), 40.2% (43/107), and 48.0% (59/123) by tumor location, respectively, but the difference among groups was not statistically significant (P>0.05). The postoperative Gleason scores were 3+3=6 in 51 cases, 3+4=7 in 98 cases, 4+3=7 in 81 cases, and ≥8 in 44 cases, with PSM rates of 19.6% (10/51), 38.8% (38/98), 45.7% (37/81) and 65.9% (29/44), respectively (P<0.001 for rate differences). The tumor burden was <30% in 157 cases, 30%-60% in 91 cases, and>60% in 26 cases, with PSM rate of 21.0% (33/157), 65.9% (60/91) and 80.8% (21/26), respectively (P<0.001 for rate differences). Moreover, there were 181 cases of pathological stage T2 (PSM rate, 29.3%) and 93 cases of pathological stage T3 (PSM rate, 65.6%), with statistical difference in PSM rates (P<0.001). The multivariable logistic regression analysis indicated that preoperative PSA >20 µg/L, postoperative Gleason score ≥8, high tumor burden and pathological stags were different between the PSM and NSM groups (P<0.05). Conclusions: The PSM of radical prostatectomy is closely related to the preoperative PSA level, the number of lesions, postoperative Gleason score, tumor burden and pathological stage. Preoperative PSA level >20 µg/L, postoperative Gleason score ≥8, high tumor burden and pathological stage are independent predictors for PSM.

[Diagnostic values of cyclin D1 immunocytochemistry and molecular testing in preoperative fine needle aspiration of undeterminate thyroid nodules].

Objective: To assess the value of cyclin D1 immunocytochemistry combined with a small panel molecular analysis in indeterminate cytological diagnosis of Bethesda category Ⅲ-Ⅴ. Methods: A consecutive cohort of 96 thyroid FNA specimens with indeterminate diagnosis (TBSRTC category Ⅲ-Ⅴ) and available histopathologic follow-up data were collected between December 2018 and December 2021 in Department of Pathology, Beijing Hospital. The cases were evaluated by cyclin D1 immunocytochemistry and molecular testing of BRAFV600E or a small panel of markers (BRAF, N-RAS, H-RAS, K-RAS and TERT) in the FNA specimens. The identification of the optimal cut-off point of cyclin D1 for the diagnosis of malignancy was evaluated using the receiver operating characteristic (ROC) curves and the assessment of the area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of all these markers were evaluated with the crosstabs and significance was calculated. Results: Ninty-six patients with 96 thyroid nodules were enrolled, including 42 cases of TBSRTC-III, 10 cases of TBSRTC-IV and 44 cases of TBSRTC-V. There were 79 females and 17 males with a median age of 47 years (range, 25 to 75 years). A 7.5% cut-off value for positive cyclin D1 nuclear immunostaining in thyroid cells demonstrated 100% PPV, 57.1% NPV, 81.0% sensitivity and 100% specificity for thyroid malignancy diagnosis. The sensitivity of the BRAFV600E mutation test or combined with a small panel test alone for thyroid malignancy diagnosis were 65.5% and 69.0% respectively. The sensitivity for thyroid malignancy diagnosis increased to 94.0% and 95.2% respectively when combining the cyclin D1 immunocytochemistry with the molecular test, and the specificities remained 100% and 91.7% respectively.The accuracy of cyclin D1 immunocytochemistry combined with a small panel of molecular test in detecting thyroid malignancy increased to 94.8% compared to using these markers alone. Conclusions: The addition of cyclin D1 immunocytochemistry and a small panel of molecular testing to FNA cytology can increase the sensitivity and NPV of cytology in indeterminate categories, and this supplementary approach provides a simple, accurate and convenient diagnostic method for reducing unnecessary thyroidectomies.

Optical design and performance of the biological small-angle X-ray scattering beamline at the Taiwan Photon Source.

The optical design and performance of the recently opened 13A biological small-angle X-ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high-flux X-rays in the energy range 4.0-23.0 keV. MoB4C double-multilayer and Si(111) double-crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high-flux beam of ∼4 × 1014 photons s-1 to a high-energy-resolution beam of ΔE/E ≃ 1.5 × 10-4; both modes share a constant beam exit. With a set of Kirkpatrick-Baez (KB) mirrors, the X-ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four-bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra-SAXS with a minimum scattering vector q down to 0.0004 Å-1, which allows resolving ordered d-spacing up to 1 µm. A microbeam, of 10-50 µm beam size, is tailored by a combined set of high-heat-load slits followed by micrometre-precision slits situated at the front-end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in-vacuum X-ray pixel detectors is installed to perform synchronized small- and wide-angle X-ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra-SAXS in one beamline.

[Three-dimensional morphology analysis of the supraosseous gingival profile of periodontally healthy maxillary anterior teeth].

OBJECTIVE: To measure the three-dimensional morphology of the labial supraosseous gingiva (SOG) and the thickness of related labial bone in maxillary anterior teeth of periodontally healthy Han nationality youth using soft tissue indirect imaging cone-beam computed tomography (CBCT). METHODS: Twenty-five periodontally healthy subjects (11 males and 14 females) with 150 maxillary anterior teeth were involved in this study. A special impression with radiopaque material including the maxillary teeth was made, then a CBCT scan with the elastomeric matrix in position was taken for each subject. The imaging data were generated and transferred to a volumetric imaging software in which three-dimensional reconstruction was conducted and the image analyses were carried out. Measurements were made at the site of labial center of the maxillary anterior teeth. The height of the SOG, the distance between cemento-enamel junction (CEJ) and bone crest, the gingival thickness at the CEJ, and the thickness of bone 2 mm below the labial bone crest were measured and the correlation analysis between the parameters was made. All the data analyses were performed using SPSS 22.0. The data were analyzed with ANVOA and Pearson correlation tests with the significance level at α=0.05. RESULTS: The mean SOG values were (3.49±0.70) mm, (3.48±0.81) mm, and (3.54±0.67) mm for central incisors, lateral incisors and canines, respectively. There were no statistically significant differences among the different sites (P > 0.05). The mean gingival thickness values were (1.45±0.23) mm, (1.13±0.24) mm, (1.14±0.22) mm for central incisors, lateral incisors and canines, respectively. The gingival thickness of the central incisors was the largest among the maxillary anterior teeth with statistically significant difference (P < 0.05). No correlation was found between the SOG and gingival thickness among the maxillary anterior teeth (P > 0.05). CONCLUSION: The gingival thickness of central incisors was the largest and the supraosseous gingival height had no correlation with gingival thickness among the periodontally healthy maxillary anterior teeth.

[Three-dimentional radiographic features of 67 maxillary radicular cysts].

OBJECTIVE: To analyze the three-dimensional radiographic characteristics of maxillary radi-cular cysts using cone-beam computed tomography (CBCT) and spiral CT. METHODS: Clinical records, histopathological reports, and CBCT or non-enhanced spiral CT images of 67 consecutive patients with maxillary radicular cysts were retrospectively acquired, and radiographic features, including size, shape, expansion, internal structure and relationship with the surrounding tissues, were analyzed. The lesions were divided into three types according to the involved tooth number, as follows: type Ⅰ (single tooth), the epicenter of the cyst was located at the apex of a nonvital tooth, without involvement of the neighbo-ring tooth; type Ⅱ (adjacent tooth involvement), the cyst was located at the apex of a nonvital tooth with involvement of the mesial and/or distal tooth root; and type Ⅲ (multi-teeth), the cyst involved the apexes of ≥4 teeth. Besides, these cysts were classified as another three types on sagittal views, as follows: centripetal, the root apex was oriented centripetally to the center of the cyst; palatal, the cyst was located mainly at the palatal side of the apex; and labial/buccal, the cyst was located mainly at the labial/buccal side of the apex. RESULTS: Totally, 67 patients with maxillary radicular cysts were acquired, including 38 males and 29 females, and their ages ranged from 13 to 77 years. Among them, 46 lesions (68.7%) were located in the anterior maxilla and 65 (97.0%) were round or oval. Labial/buccal cortex expansion was present in 43 cases (64.2%) and palatal cortex expansion in 37 cases (55.2%). The nasal floor was invaded in 27 cases (40.3%), the maxillary sinus was invaginated in 26 cases (38.8%), and root resorption was present in 9 cases (13.4%). The average diameter of lesions was (20.89±8.11) mm mesio-distally and (16.70±5.88) mm bucco-palatally. In spite of the 4 residual cysts, the remaining 63 lesions included 14 type Ⅰ, 26 type Ⅱ and 23 type Ⅲ cysts according to the involved tooth number. Besides, the 63 lesions included 46 centripetal, 15 palatal and 2 buccal cysts on sagittal views. CONCLUSION: The maxillary radicular cysts were frequently well-circumscribed round or oval radiolucency, with significantly different sizes. According to the involved tooth number, it can be divided into single tooth, adjacent tooth involvement and multi-teeth types. On sagittal views, the root-cyst relationship was centripetal in most cases, while a minority of cysts expanded palatally or buccally.

[Application of cell transfer technique in the diagnosis of fine needle aspiration cytology].

Objective: To study the application of cell transfer technology to solve the problem of the limited number of fine needle aspiration cytology (FNAC) smears for various immunocytochemistry (ICC) staining and other auxiliary tests, and to enhance accurate cytological diagnosis. Methods: Thirty-four cases of FNAC smears from January 2020 to April 2020 in the Department of Pathology of Beijing Hospital were collected for investigation of the cell transfer technique. The materials in the most cell smear were divided and transferred to several glass slides. After de-staining, the recipient slides were stained with EnVision ICC. The technique was validated by comparing the consistency of the ICC of transferred cell smears and the corresponding immunohistochemical (IHC) staining on biopsies. Results: There were a total of 180 cell transfer slides from 34 cases, of which 174 had the same cell morphology, size and structure as the original smears, with the success rate of cell transfer of 96.7% (174/180). Totally 174 ICC stains were performed on the successfully transferred cell smears, of which 153 smears had available corresponding IHC staining of histologic specimens. Of these, 148 showed concordance between ICC staining and the IHC staining. Cells were successfully transferred in 96.7 % (148/153) of the cell sheets, keeping the same morphology and structure as compared to their original smears. The diagnosis of all 34 FNAC cases was the same to that of their corresponding pathology on biopsies with 100 % concordance. Conclusions: The cell transfer technique is a simple and effective way to make full use of diagnostic cells on a cell smear, and is valuable for accurate cytological diagnosis.

[Whole genomic copy number variation score: an indicator of potential diagnostic and prognostic value for lung adenocarcinoma].

Objective: To verify the value of whole genomic copy number variation (WGCNV) detection and scoring system in the diagnosis and prognosis of lung adenocarcinoma. Methods: Seventy-six lung adenocarcinoma specimens including ninety-one tumor samples and twenty adjacent non-tumor lung tissue samples were collected using Laser capture microdissection (LCM). Whole genomic amplification (WGA) was used to enrich DNA and construct a sequencing library for next generation sequencing (NGS). Changes of larger than 5Mb CNV in this study were analyzed and scored. The nuclear grading and score of tumor cells in the surgery and pleural effusion cytology of lung adenocarcinoma specimens were evaluated separately. For each case, we evaluated (1) nuclear size, (2) mitotic counts, (3) nuclear atypia, (4) atypical mitoses. The data of disease-free survive (DFS) and overall survive (OS) were collected for assessing the prognostic value of WGCNV score. Meanwhile, receiver operating characteristic (ROC) and area under curve (AUC) were used to define a cut-off value and evaluate the diagnostic significance in lung adenocarcinoma. Results: The WGCNV scores of twenty adjacent non-tumor lung tissue samples were treated as normal control and all of WGCNV scores of tumor samples range from 0 to 9.95, the median score was 2.7. The WGCNV scores were divided into three groups: low score group <1.74, medium score grade 1.74~4.23, high score grade >4.23. The WGCNV score was positively associated with the nuclear grade scoring (r=0.780 90, P<0.001). The result for evaluation of prognostic value of the WGCNV scores showed that comparing with low WGCNV score group, Hazard Ratio (HR) of medium score group was 4.11 (95%CI=0.72~23.57) and high score group was 2.07 (95%CI=0.30~14.12). These results suggested that the risks of the medium and high WGCNV score group elevated. According to the analysis results of ROC curve, when the cut off value was 0.01, the sensitivity and specificity for lung adenocarcinoma diagnosis were 97.8% and 95.0% respectively, the positive predictive value (PPV) and negative predictive value (NPV) were 99.0% and 90.1%, respectively, the AUC was 0.981. In the differentiation of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) group and invasive adenocarcinoma group, when the cut off value was 1.8, the sensitivity and specificity between the two groups were 78.1% and 94.4%, and the PPV and NPV were 98.0% and 52.0%, respectively, the AUC was 0.896. Conclusion: This study verifies that WGCNV scoring system has a potential diagnostic and prognostic value in lung adenocarcinoma.

[Inflammation grading and sialoendoscopic treatment of 131I radioiodine-induced sialadenitis].

OBJECTIVE: To investigate the inflammation grading of 131I radioiodine-induced sialadenitis based upon sialoendoscopic and sialographic appearances, and to evaluate the results of sialoendoscopic intervention. METHODS: The patients diagnosed with 131I radioiodine-induced sialadenitis and underwent sialoendoscopic exploration and intervention procedures in Peking University Hospital of Stomatology from Nov. 2012 to Oct. 2018 were included in this study. The appearances of sialogaphy and sialoendoscopy were analyzed and classified. The treatment options included irrigation with saline and dexamethasone and mechanical dilatation by sialoendoscope. The patients were followed up after treatment. RESULTS: Forty-two patients with 131I radioiodine-induced sialadenitis were included. There were 5 males and 37 females, with a male-to-female ratio of 1 ∶7.4. Symptoms included recurrent swelling and pain in the parotid glands, and dry mouth. Sialography showed stenosis in the main duct,and in some cases nonvisua-lization of the branches. Sialoendoscopy showed narrowing of the main duct, and the branch duct atresia was seen. The appearances of sialogaphy and sialoendoscopy were analyzed and classified into 3 groups: (1) Mild inflammation: stenosis and ectasia occurred in the main duct, whereas the 0.9 mm sialoendoscope could pass through easily. (2) Moderate inflammation: one point of severe stricture could be seen in the main duct where 0.9 mm sialoendoscope could not be passed through. (3) Severe inflammation: two points or more of severe strictures or diffused strictures occurred in the main duct. Thirty-three patients with 65 affected glands were examined by both sialography and sialoendoscopy. Eight glands were classified as mild inflammation, 23 glands moderate inflammation, and 34 glands severe inflammation. The duration of follow-up ranged from 3-72 months. The clinical results were evaluated as good in 22 glands, fair in 22 glands, and poor in 19 glands, with an overall effective rate of 69.8% (44/63). CONCLUSION: The clinical, sialographic and sialoendoscopic appearances of 131I radioiodine-induced sialadenitis showed their characteristics. We proposed an inflammation grading standard for the 131I radioiodine-induced sialadenitis based on the appearances of sialography and sialoendoscopy. Sialoendoscopy can significantly alleviate the clinical symptoms, which is an effective therapy, and better for early lesions.

[Phase â ¢ randomized controlled, multicenter, prospective study of recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine in patients with HER2 positive metastatic breast cancer: the HOPES Study].

Objective: To evaluate the clinical efficacy and safety of recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine in patients with HER2 positive metastatic breast cancer. Methods: Patients were randomized 2∶1 to test group and control group. Patients in test group received Cipterbin (4 mg/kg loading dose and 2 mg/kg maintenance dose each week, IV) combined with vinorelbine (25 mg/m(2) on days 1,8 and 15 of each 28 days, IV). Patients in control group received vinorelbine (25 mg/m(2) on days 1,8 and 15 of each 28 days, IV).The primary end point was progression free survival (PFS). Results: A total of 315 patients were enrolled from Jan 2009 to Jan 2013 (212 in test group and 103 in control group). The median PFS of test group was significantly longer than that of control group, 39.1 weeks vs 14.0 weeks (HR=0.24; 95%CI, 0.16-0.36; P<0.000 1). The objective response rate (ORR) and disease control rate (DCR) in test group were significantly higher than those in control group, ORR was 46.7% vs 18.45% (P<0.000 1) and DCR was 79.72% vs 45.63% (P<0.000 1). The incidence of neutropenia, leucopenia and erythrocytopenia were higher in both groups, but there was no significant difference between two groups.The most common adverse events associated with Cipterbin were infusion reactions. Left ventricular ejection fraction reduced to less than 50% in 5 patients, which were recovered. No serious cardiotoxicity. Conclusion: The recombinant anti-HER2 humanized monoclonal antibody (Cipterbin) combined with vinorelbine has significant efficacy and good safety. It is the optimized therapy regime for patients with taxane-pretreated HER2 positive metastatic breast cancer, which provides more targeted therapy opportunities for HER2 positive breast cancer patients in China.

[The co-relation of BRAF V600E mutation and factors affecting occurrence and prognosis of papillary thyroid carcinoma].

Objective: To investigate the prevalence of BRAF V600E mutation in thyroid nodules and to analyze the relationship between BRAF V600E mutation and various clinicopathological features. Methods: BRAF V600E mutant gene test was done in 463 cases of thyroid nodules collected from April 2015 to July 2018 in Beijing Hospital. Pathologic sections of 444 cases of papillary thyroid carcinoma were reviewed and clinical information was collected.Statistical analysis of the relationship between BRAF V600E gene mutation and various clinicopathological features was performed with SPSS 21.0 statistical software. Results: There were 109 males and 354 females in the cohort, with a male to female ratio of 1.0∶3.2. The patient ranged in age from 16 to 82 years, with an average age of 46.1 years. The BRAF V600E mutation rates in papillary thyroid carcinoma, benign thyroid nodules and other thyroid carcinoma were 86.5%(384/444),0/15 and 1/4,respectively.There was significant correlation between BRAF V600E mutation and histological diagnosis of papillary thyroid carcinoma (P<0.05). There was no correlation with age, gender, multifocality, bilaterality, coexisting lymphocytic thyroiditis, nodular goiter, maximum diameter, capsule invasion, extrathyroidal extension and clinical stage (P>0.05). Conclusions: BRAF V600E gene mutation is closely related to the occurrence of papillary thyroid carcinoma. BRAF V600E has significant value in the diagnosis of papillary thyroid carcinoma. While BRAF V600E mutation is related to the histological diagnosis, it shows no correlation with other clinicopathologic features. BRAF V600E mutation is not an independent prognostic factor in papillary thyroid carcinoma patients.

[Diagnosis of lung biopsy employing the 2015 WHO criteria and detection of related oncogenic driver mutations].

Objective: The diagnostic criteria of lung biopsy specimens by 2015 WHO lung tumor classification were used to evaluate lung biopsy specimens along with detection of genetic alterations of major tumor driving genes including epidermal growth factor receptor (EGFR). Methods: The clinical data, histological slides, immunohistochemical stains and special stains of 806 lung biopsy specimens at Beijing Hospital from July 2015 to July 2018 were retrospectively analyzed. Diagnosis of lung cancer was reclassified according to the 2015 WHO lung tumor classification and related gene mutation data were analyzed. Results: During a three-year period, the total number of lung cancer diagnosis was 483 cases, including 221 female and 262 male patients with age ranging from 37 to 85 years (median age of 65 years). There were 40 cases(8.28%) of small cell carcinoma,11 cases (2.28%) of large cell neuroendocrine carcinoma, 3 cases (0.62%) of combined neuroendocrine carcinoma, 2 cases(0.41%) of atypical carcinoid, 208 cases (43.06%) of adenocarcinoma, 92 cases(19.05%) of non-small cell carcinoma, favor adenocarcinoma, 66 cases (13.66%) of squamous cell carcinoma, 42 cases(8.70%) of non-small cell carcinoma, favor squamous cell carcinoma, 16 cases(3.31%) of non-small cell carcinoma, not otherwise specified, and 3 cases (0.62%) of non-small cell carcinoma, possible adenosquamous carcinoma. Among 202 cases tested, 107 cases (52.97%) showed EGFR mutations, including 86 of 133 cases (64.66%) of adenocarcinoma and 18 of 52 cases (34.62%) of non-small cell carcinoma, favor adenocarcinoma. Twenty two cases were found to have T790M mutation among 27 patients after EGFR TKI targeted drug therapy. Immunohistochemical staining of ALK (D5F3) was positive in 3 of 354 cases of non-small cell lung cancer, confirmed by EML4-ALK fusion gene fluorescence PCR. ROS1 gene fusion was found in 1 of 38 cases. Splicing mutations in exon 14 of MET gene were seen in one case of non-small cell carcinoma with spindle cell differentiation. Conclusion: The new diagnostic criteria by the 2015 WHO lung tumor classification is better suited for diagnosing lung biopsy specimens and providing accurate treatment guidance and improving the patient outcome.

An algorithmic approach to diagnose haematolymphoid neoplasms in effusion by combining morphology, immunohistochemistry and molecular cytogenetics.

OBJECTIVE: There are limited studies of cytology diagnosis of haematopoietic and lymphoid tumours in serosal effusion except for occasional case reports. We would like to demonstrate an algorithmic approach for accurate diagnosis, especially in patients without previous history. METHODS: We reviewed 36 cases of lymphoma diagnosed in serosal effusion following an algorithmic approach. Suspected tumour cells were classified into small, intermediate and large sizes and two characteristic forms of plasmacytoid and Reed Sternberg-like on smears (step 1), followed by utilising panels of immunohistochemical markers and Epstein-Barr encoding region in situ hybridisation on cell blocks (step 2). A panel of CD3, CD20 and Ki-67 formed the basic workup, followed by pertinent batteries of immunostaining. Molecular tests were applied in 22 selected cases by fluorescence in situ hybridisation (step 3). RESULTS: There were 15 diffuse large B-cell lymphomas; 12 plasma cell myelomas; two mantle cell lymphomas; one anaplastic large cell lymphoma ALK +; one small lymphocytic lymphoma; one plasmablastic lymphoma; one peripheral T-cell lymphoma, not otherwise specified, one extranodal NK/T-cell lymphoma, nasal type and two T-cell lymphoblastic lymphomas. 14 cases with previous history had complete concordance in immunophenotype between cytology and histology. Another 14 cases were primarily diagnosed in patients with initial symptom of effusion based on immunophenotyping and cytogenetic test in selected cases. Eight cases were diagnosed based on morphology alone. CONCLUSION: An algorithmic approach based on morphology and immunohistochemistry is the key to making an accurate diagnosis of haematopoietic and lymphoid tumours in effusion. A molecular test is also important for confirmation and prognostic prediction. We reviewed 36 haematolymphoid neoplasms diagnosed in effusion including 14 cases primarily diagnosed in patients without previous history following an algorithmic approach by combining morphology, immunohistochemistry and molecular cytogenetics.

[Evaluation of Consistency in detection of epidermal growth factor receptor gene T790M mutation in plasma and tumor specimens of patients with lung adenocarcinoma].

Objective: To evaluate the consistency in detection of T790M mutation of epidermal growth factor receptor gene (EGFR) in plasma and tumor samples of patients with lung adenocarcinoma. Methods: The tumor tissues or cytological specimens of 12 patients with operable lung adenocarcinoma(stage Ⅰ-ⅢA) and 100 patients with advanced stage ⅢB-Ⅳ lung adenocarcinoma were collected, among which 11 patients showed acquired resistance for gefitinib (11/100). In the same period, peripheral blood samples were collected from all patients and 50 healthy volunteers. Amplification refractory mutation system (ARMS) was used to detect EGFR mutations in tumor specimens. Next Generation Sequencing(NGS) based circulating single-molecule amplification and resequencing technology (cSMART)was performed to quantitatively detect the EGFR mutations in circulating tumor DNA (ctDNA) from plasma specimens. Results: The sensitivity, specificity and concordance rate of EGFR T790M mutation between plasma and tissue specimens from 100 advanced stage patients were 50.0%, 72.9% and 72.0%, respectively. For L858R mutation and exon 19 deletion mutations, the above mentioned sensitivity, specificity and concordance rate were 91.7%, 100.0%, and 98.0%, as well as 79.2%, 100.0% and 95.0%, respectively. The L858R mutation and exon 19 deletion mutations were not detected in plasma of 50 healthy volunteers, whereasT790M mutation(1.0±0.0 copies) was found in 7 individuals(7/50, 14.0%). Similarly, in 12 resectable patients, 4 (4/12, 33.3%) T790M mutations were found in plasma (1.2±0.2 copies), but no L858R mutation and 19 exon deletion mutations. In comparison, 28.0% of patients with advanced lung adenocarcinoma (28/100)had detectable T790M mutation in plasma with copy numbers (34.0±22.7 copies). Furthermore, the copy numbers of T790M were 268.2±119.9 in plasma of 5 cases with acquired gefitinib-resistance. Conclusions: In patients with advanced stages of lung adenocarcinoma, the detection of T790M mutation in plasma and tumor specimens is low. The T790M mutation also exists in the plasma of some healthy controls, suggesting that T790M mutation participates in EGFR signaling pathway and it might function in healthy population.