Diagnostic values of nuclear score combined with cyclin D1 immunocytochemistry in indeterminate thyroid follicular nodules in preoperative fine needle aspiration / 中华病理学杂志

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.

Retrospective analysis of BI-RADS 4 and 5 lesions additionally detected by breast MRI / 中华外科杂志

Objectives: To establish a newly-designed scoring system for breast imaging-reporting and data system (BI-RADS) 4 and 5 breast lesions only visible on MRI, and to examine their clinical pathway of biopsy. Methods: The BI-RADS 4 and 5 breast lesions only visible on MRI but not suspected on mammograms or ultrasound between June 2007 and December 2021 at Beijing Hospital were evaluated retrospectively. A total of 209 lesions from 184 patients were finally included. All patients were female, aged (50±11) years (range: 27 to 76 years). All lesions were confirmed by pathology and divided into malignancy and non-malignancy. The lesions were divided into mass and non-mass type using BI-RADS. The receiver operator characteristic (ROC) curve was used to evaluate the diagnostic performance of the new scoring system. Four types of pathology-obtaining pathway were used: biopsy guided by second-look ultrasound, local excision guided by lesion position information on MRI, intraductal lesion excision guided by methylene blue stain and mastectomy. The data between mass and non-mass lesions were compared by Mann-Whitney U test, χ2 test or Fisher exact test,respectively. Results: There were 124 malignant and 85 non-malignant lesions, while 100 mass and 109 non-mass lessions. The sizes between mass and non-mass lesions showed significant difference(M(IQR)) (7.0 (3.0) mm vs. 25.0 (25.0) mm, U=568.000, P<0.01) and their BI-RADS diagnostic accuracy had no significant difference (53.0% (53/100) vs. 65.1% (71/109), χ2=3.184, P=0.074). The areas under ROC curve of the new scoring system for evaluating mass and non-mass were 0.841 and 0.802, respectively. When taking Score 3 as threshold, it can potentially avoid 14.0% (14/100) and 4.6% (5/109) of biopsies in mass and non-mass, respectively. As to pathway of obtaining pathology, second-look ultrasound succeeded more easily in mass than non-mass (41.0% (41/100) vs.26.6% (29/109), χ2=4.851, P=0.028). More MRI-guided local excisions were performed in non-mass than mass (52.3% (57/109) vs. 34.0% (34/100), χ2=7.100, P=0.008). Conclusions: For suspicious breast lesions detected by MRI but not suspected on X-ray or ultrasound, the new scoring system can further increase diagnostic accuracy. The second-look ultrasound plays an important role for obtaining pathology, especially for mass-type lesion.

Pathological characteristics of coronary artery disease in elderly patients aged 80 years and over / 中华心血管病杂志

<p><b>OBJECTIVE</b>To define the pathological changes of coronary artery and compare the clinical diagnosis and pathological diagnosis differences in elderly patients aged 80 and over.</p><p><b>METHODS</b>A total of 909 autopsy cases aged 60-100 years in our hospital from April 1st 1969 to October 31th 2013 were analyzed. The prevalence and pathological features of coronary artery disease (CAD) in cases aged 80 years and over were compared with those aged 60-79 years old. The misdiagnosis and missed diagnosis rate were calculated.</p><p><b>RESULTS</b>The prevalence of CAD by autopsy (63.8% (289/453) vs. 39.9% (182/456), P<0.01), old myocardial infarction (OMI) by autopsy (63.0% (182/289) vs. 51.6% (94/182), P<0.05) and chronic myocardial ischemia by autopsy (22.5% (65/289) vs. 7.1% (13/182), P<0.01) were significantly higher while the prevalence of acute myocardial infarction (AMI) by autopsy was significantly lower (22.1% (64/289) vs. 42.9% (78/182), P<0.01) in aged 80 and over group compared to 60-79 years old group. The misdiagnosis rate of CAD was 65.2% (107/164), the missed diagnosis rate of OMI was 62.1% (113/182) and the missed diagnosis rate of AMI was 37.5% (24/64) in the aged 80 and over group.</p><p><b>CONCLUSIONS</b>The prevalence of CAD and misdiagnosis and missed diagnosis rate are high in dead inpatients aged 80 years and over. OMI is more common but often missed in this group. Thus, the diagnosis and evaluation of CAD should be enhanced in this patient group.</p>

Cytodiagnosis and cytomorphologic analysis of hematolymphoid malignancy in serous effusion: a study of 23 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the value of cytomorphologic and immunocytochemical approaches in the diagnosis of hematologic neoplasms in serous effusion.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Expression of cytokine IL-1α and S100β in different types of plaques in Alzheimer's disease / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the significance of cytokine IL-1α and S100β expression in formation and evolution of different types of plaques in Alzheimer's disease.</p><p><b>METHODS</b>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/Aβ and S100β/Aβ.</p><p><b>RESULTS</b>Immunohistochemical studied for IL-1α/Aβ and S100β/Aβ 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 S100β-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 S100β-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 S100β-positive astrocytes associated with diffuse neuritic plaques were significantly higher than those of the other three types of plaques (P < 0.05).</p><p><b>CONCLUSION</b>The IL-1α-positive microglias and S100β-positive astrocytes may be of certain significance in transformation of diffuse non-neuritic plaques to diffuse neuritic plaques in Alzheimer's disease.</p>

Treatment of platinum-resistant recurrent ovarian cancer using a "predictive molecule targeted routine chemotherapy" system / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>The predictive molecule targeted routine chemotherapy is a new effective protocol for choosing drugs when treating platinum-resistant recurrent ovarian cancer.</p>

Expression of apolipoprotein E in Alzheimer's disease and its significance / 中华病理学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Relationship between apoptosis of neurons and microglia activation in Alzheimer's disease / 中华病理学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Imaging characteristics of autoimmune pancreatitis / 中华放射学杂志

Objective To investigate the imaging characteristics of autoimmune pancreatitis (AIP).Methods MR imaging was performed in 12 patients with AIP proved histopathologically or clinically,of them CT was scanned in 10 patients and endoscopic retrograde cholangiopancreatography (ERCP)in 3.All imaging data were reviewed retrospectively.Results All 12 patients had enlargement of the pancreas either diffusely(n=9)or focally(n=3).The swollen pancreas was hypointense on T_1-weighted images and mildly hyperintense on T_2-weighted images.It also demonstrated decreased enhancement on artery phase of dynamic imaging and moderate enhancement on delayed phase images. Capsule-like enhanced rim was found around the swollen pancreas in 11 patients.Stricture of the distal common bile duct was found in 9 patients,and ERCP showed diffuse and irregular narrowing of the main pancreatic duct in 3 cases.At follow-up,pancreatic abnormalities and common bile duct stricture resolved after steroid therapy in 7 patients.Conclusion AIP showed some characteristic imaging findings,and imaging examinations will play an important role in the diagnosis of AIP.