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Objective:To examine the clinicopathological and molecular pathological characteristics of patients with colorectal cancer(CRC)who have mutations in the POLE and POLD1 genes.Methods:In this study, we retrospectively collected data from 276 middle-aged and elderly patients aged 45 years and over who were diagnosed with colorectal cancer at Beijing Hospital between October 2020 and September 2022.We utilized next generation sequencing and bioinformatics analysis to screen for harmful germline and somatic mutations in the POLE and POLD1 genes.The study involved 276 patients, who were divided into three groups based on their genetic mutations.The deleterious mutation group had 6 cases, the mutation of unknown significance group had 18 cases, and the wild type group had 252 cases.We also collected clinical and pathological features of the patients and analyzed their correlation with other molecular pathological results such as tumor mutation burden(TMB), microsatellite instability(MSI), and gene co-mutation.Results:No germline mutations were detected in the POLE and POLD1 genes across all patients.Out of the 276 patients, 18(6.5%)were found to carry POLE mutations.Among these, 6(2.2%)were classified as deleterious mutations, 12(4.3%)were positive for POLE mutations of unknown significance, and the remaining patients had wild type POLE genes.Out of the 276 patients, POLD1 gene mutations of unknown significance were found in 10 patients(3.6%). Among the 276 patients, 5 cases(1.8%)carried two types of gene mutations.Patients in the deleterious mutation group showed earlier tumor stage( P<0.05)and a higher prevalence of low-grade tumor budding( P<0.05), with 6 patients being affected by this.Compared to the wild type group, colon cancer patients showed a higher frequency of deleterious mutations and variants of unknown significance in the poorly differentiated group( P<0.05). The median TMB in the deleterious mutation group was 257.76 muts/Mb, 74.4 muts/Mb in the mutation of unknown significance group, and 5.81 muts/Mb in the wild type group.The study found significant differences in TMB-H status among the three groups, with all P-values less than 0.01.MSI-H status was detected in 1 case(16.7%, 1/6), 14 cases(77.8%, 14/18), and 18 cases(7.1%, 18/276)in the deleterious mutation group, variant of undetermined significance group, and wild type group, respectively.Notably, patients with variants of undetermined significance had a higher MSI-H status than patients with wild type and POLE deleterious mutations, with all P-values less than 0.01.The frequencies of co-mutations in KRAS, NRAS, BRAF, and PIK3CA were higher in the deleterious mutation group compared to the mutation of undetermined significance group and wild type group(all P<0.05). Conclusions:Colorectal cancer(CRC)patients with harmful mutations and variants of undetermined significance exhibit unique clinicopathological features.Patients with variants of undetermined significance are more likely to develop colon cancer, show poor differentiation, and have higher frequencies of TMB-H(tumor mutational burden)and MSI-H(microsatellite instability-high).
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Objective:To investigate the features of volume, distribution, grading and staging of prostate cancer(PCa)examined via whole-mount histopathology in transitional PCa.Methods:A total of 129 PCa patients undergone radical prostatectomy(RP)between July 2017 and March 2020 whose whole-mount prostate specimens were prepared after surgery were retrospectively studied.Pathological data on tumor locations, diameters and classification of the International Society of Urologic Pathology(ISUP), radiological data on regions of interest(ROI)and scores of the Prostate Imaging and Reporting Data System(PI-RADS v2)were recorded.The results of pathological whole-mount sections and prostate imaging were compared, and the characteristics and detection rates of lesions in different prostate regions were analyzed.Results:Of all 129 prostate specimens from RP, a total of 213 PCa lesions were detected through whole-mount histopathology.There were 21(9.9%)lesions involving both the peripheral zone(PZ)and the transition zone(TZ), with an average diameter of(2.82±0.71)cm.Of all lesions, 85(39.9%)involved PZ and 107(50.2%)involved TZ, with an average diameter of(1.36±0.81)cm and of(1.60±0.94)cm, respectively.The percentage of lesions involving TZ was higher than that lesions involving PZ, with larger diameters( P<0.05). Of 64 patients with complete MRI data, 105 PCa lesions were detected histopathologically by using whole mount sections, while 75 PCa lesions were detected by MRI, with a statistical difference( P<0.05). For lesions≥1.0 cm or lesions with an ISUP grade group≥2, the detection rate of MRI was lower in TZ lesions( P<0.05). Conclusions:PCa lesions within TZ account for a large proportion and have a relatively large tumor dimeter.PCa lesions within TZ are more likely to be missed in clinical examinations and on MRI, and clinicians should pay close attention during diagnosis and treatment.
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Objective@#To study on the diagnostic value of non-tumor lung biopsy by the multidisciplinary discussion including clinician, radiologist and pathologist.@*Methods@#Clinical data, imaging data and data of hematoxylin-eosin, immunohistochemical and special staining of pathological lung tissues in 217 cases undergoing non-tumor lung biopsy in Beijing Hospital during July 2015 to July 2018 were retrospectively analyzed.The diagnosis results were summarized and analyzed.@*Results@#The age range in 217 cases was 45-89 years, and the median age was 67 years, with 92 females and 125 males.The descriptive diagnoses were found in forty-two cases(19.4%, 42/217). And 175 cases could be confirmatively diagnosed by the multidisciplinary discussion of clinician, radiologist and pathologist.And the diagnostic rate of lung puncture biopsy was 80.6%(175/217 cases). Inflammatory lesions were divided into infection and non-infection.A total of 68 infection cases(31.3%, 68/217)included tuberculosis(43/68, 63.2%), bacterial pneumonia(14/68, 20.6%)and fungal infection(11/68, 16.2%). A total of 107 cases(49.3%, 107/217)of non-infective cases included the following: organized pneumonia(53/107, 49.5%), interstitial pneumonia with autoimmune features(iPAF)(16/107, 15.0%), nonspecific interstitial pneumonia(NSIP)(13/107, 12.1%), hypersensitivity pneumonitis(8/107, 7.5%), granulomatosis with polyangiitis(GPA)(4/107, 3.7%), eosinophilic pneumonia(2/107, 1.9%), sarcoidosis(2/107, 1.9%), acute fibrinous and organizing pneumonia(AFOP)(2/107, 1.9%)and coal pneumoconiosis(2/107, 1.9%, for each), and IgG4 related diseases(1/107, 0.9%), pleuraparenchymal fibroelastomatosis(PPFE)(1/107, 0.9%), asbestos lung(1/107, 0.9%), lipid pneumonia(1/107, 0.9%)and inhaled pneumonia(1/107, 0.9%).@*Conclusions@#The diagnoses of the puzzled non-tumor lung diseases were more accurate by pathological examination of lung tissue by using special stain, immunohistochemical stain and other pathological means, and by close multidisciplinary consultation of clinician, radiologist and pathologist, so as to facilitate the diagnosis and treatment of diseases.
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Objective@#To analyze the clinical and pathological characteristics of heart failure with preserved ejection fraction(HFpEF)in advanced elderly patients.@*Methods@#Systematic anatomical data from pathology database of Beijing Hospital from April 1969 to October 2013 were retrospectively analyzed.The 154 HFpEF patients aged(85.7±7.4)years with left ventricular ejection fractions(LVEF)≥50%, and 49 patients aged(82.8±7.8)years who had heart failure with reduced LVEF ≤40%(HFrEF)were included.Clinical feature and pathological changes of heart and other organs were compared between patients with HFpEF and HFrEF, and between groups aged less 80 years versus over 80 years in HFpEF patients.@*Results@#The parameters were higher in HFpEF group versus in HFrEF group as follows: the average age of patients(85.7±7.4 vs.82.8±7.8 years, P=0.017), hypertension(80.5% or 124 cases vs.26.5% or 13 cases, P<0.001), diabetes mellitus(58.4% or 90 vs.20.4% or 10 cases, P<0.001), atrial fibrillation(65.6% or 101 cases vs.12.2% or 6 cases, P<0.001)and chronic obstructive pulmonary disease(COPD)(26.6% or 41 cases vs.4.1% or 2 cases, P=0.001). As compared with HFpEF patients aged 61-85 years group, the same HFpEF patients aged 86-99 years group had significantly increased proportion of atrial fibrillation(P=0.046), of COPD(P=0.002), of senile degenerative heart valvular disease(P=0.009), of chronic myocardial ischemia(P=0.027), of mini-focal old myocardial infarction(P=0.041)and of emphysema(P=0.005).@*Conclusions@#The proportion of patients with HFpEF increases along with ageing.Atrial fibrillation and COPD are common geriatric co-morbidities in the elderly especially advanced elderly HFpEF patients.The patients are prone to complicated with atrial fibrillation and COPD, and often have chronic myocardial ischemia.Therefore, we should pay attention to the influences of the above diseases on elderly patients with HFpEF.
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Objective To analyze the clinical and pathological characteristics of heart failure with preserved ejection fraction (HFpEF)in advanced elderly patients.Methods Systematic anatomical data from pathology database of Beijing Hospital from April 1969 to October 2013 were retrospectively analyzed.The 154 HFpEF patients aged(85.7± 7.4)years with left ventricular ejection fractions(LVEF) ≥50％,and 49 patients aged(82.8± 7.8)years who had heart failure with reduced LVEF ≤ 40％ (HFrEF)were included.Clinical feature and pathological changes of heart and other organs were compared between patients with HFpEF and HFrEF,and between groups aged less 80 years versus over 80 years in HFpEF patients.Results The parameters were higher in HFpEF group versus in HFrEF group as follows:the average age of patients(85.7±7.4 vs.82.8±7.8 years,P=0.017),hypertension(80.5％ or 124 cases vs.26.5％ or 13 cases,P ＜0.001),diabetes mellitus (58.4％ or 90 vs.20.4％ or 10 cases,P＜0.001),atrial fibrillation(65.6％ or 101 cases vs.12.2％ or 6 cases,P＜0.001)and chronic obstructive pulmonary disease(COPD)(26.6％ or 41 cases vs.4.1％ or 2 cases,P=0.001).As compared with HFpEF patients aged 61-85 years group,the same HFpEF patients aged 86-99 years group had significantly increased proportion of atrial fibrillation(P =0.046),of COPD(P =0.002),of senile degenerative heart valvular disease(P =0.009),of chronic myocardial ischemia(P =0.027),of mini-focal old myocardial infarction (P =0.041) and of emphysema (P =0.005).Conclusions The proportion of patients with HFpEF increases along with ageing.Atrial fibrillation and COPD are common geriatric co-morbidities in the elderly especially advanced elderly HFpEF patients.The patients are prone to complicated with atrial fibrillation and COPD,and often have chronic myocardial ischemia.Therefore,we should pay attention to the influences of the above diseases on elderly patients with HFpEF.
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Objective To study on the diagnostic value of non-tumor lung biopsy by the multidisciplinary discussion including clinician,radiologist and pathologist.Methods Clinical data,imaging data and data of hematoxylin-eosin,immunohistochemical and special staining of pathological lung tissues in 217 cases undergoing non-tumor lung biopsy in Beijing Hospital during July 2015 to July 2018 were retrospectively analyzed.The diagnosis results were summarized and analyzed.Results The age range in 217 cases was 45-89 years,and the median age was 67 years,with 92 females and 125 males.The descriptive diagnoses were found in forty-two cases(19.4％,42/217).And 175 cases could be confirmatively diagnosed by the multidisciplinary discussion of clinician,radiologist and pathologist.And the diagnostic rate of lung puncture biopsy was 80.6％ (175/217 cases).Inflammatory lesions were divided into infection and non infection.A total of 68 infection cases (31.3％,68/217) included tuberculosis (43/68,63.2％),bacterial pneumonia (14/68,20.6％) and fungal infection(11/68,16.2％).A total of 107 cases(49.3％,107/217)of non-infective cases included the following:organized pneumonia(53/107,49.5 ％),interstitial pneumonia with autoimmune features (iPAF) (16/107,15.0 ％),nonspecific interstitial pneumonia(NSIP) (13/107,12.1％),hypersensitivity pneumonitis(8/107,7.5％),granulomatosis with polyangiitis (GPA) (4/107,3.7％),eosinophilic pneumonia (2/107,1.9％),sarcoidosis (2/107,1.9％),acute fibrinous and organizing pneumonia (AFOP) (2/107,1.9 ％) and coal pneumoconiosis (2/107,1.9 ％,for each),and IgG4 related diseases (1/107,0.9％),pleuraparenchymal fibroelastomatosis (PPFE) (1/107,0.9％),asbestos lung(1/107,0.9％),lipid pneumonia(1/107,0.9％) and inhaled pneumonia(1/107,0.9％).Conclusions The diagnoses of the puzzled non-tumor lung diseases were more accurate by pathological examination of lung tissue by using special stain,immunohistochemical stain and other pathological means,and by close multidisciplinary consultation of clinician,radiologist and pathologist,so as to facilitate the diagnosis and treatment of diseases.
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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.
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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.
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Objective To study the detection protocol of epidermal growth factor receptor (EGFR)gene mutations in cerebrospinal fluid(CSF)specimens of lung adenocarcinoma by establishing a liquid biopsy technique,and to analyze clinical value of the detection findings for clinical therapy.Methods In the retrospective study,a total of 26 CSF specimens from lung adenocarcinoma patients who harbored EGFR gene mutations(L858R and EGFR exon 19 deletion)were collected.The included patients were treated with first-generation EGFR TKIs,and had brain metastasis detected by imaging examinations.Five CSF specimens from non-tumor patients confirmed by clinical findings and cytological and pathological diagnosis were collected during the same period.EGFR gene mutations in cell-free CSF supernatant fluid were detected by using the protocol recommended in this study.Results EGFR mutations were detected in 21/26 (80.8％)of cell-free supernatants from CSF specimens of lung adenocarcinoma patients,including 13 cases(61.9％)with EGFR L858R mutations and 8 cases(38.1％)with EGFR exon 19 deletion.No T790M mutation was detected in cell-free supernatants from all CSF specimens.No EGFR mutation was detected in cell-free supernatants from all CSF specimens from non-tumor patients.Conclusions Our study-established protocol could be used to detect EGFR mutations in cell-free supernatants from CSF specimens with high sensitivity and specificity.Perhaps due to the characteristics of first-generation EGFR TKIs,the detection rate of T790M mutation is low.The detection of T790M mutation in cell-free supernatants from CSF specimen may have a limited clinical value for choice of 3rd generation EGFR TKIs.
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Objective@#To study the histological subtyping of poorly differentiated solid lung cancer by using immunohistochemistry and mucin staining along with analysis of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene rearrangement.@*Methods@#Among 827 cases of non-small cell lung cancer at Beijing Hospital from April 2014 to April 2017, 167 cases of solid poorly differentiated lung cancer were identified and histopathologically subtyped by mucin staining (D-PAS) and immunohistochemistry using 10 antibodies (CK7, vimentin, Ki-67, CK5/6, p40, TTF1, Napsin A, CD56, chromogranin A, and synaptophysin). Paraffin embedded tumor samples were subjected to mutation analysis of exons 18, 19, 20 and 21 of the EGFR gene by amplification refractory mutation system (ARMS) method. Immunohistochemistry (Ventana D5F3) for ALK gene rearrangement was performed followed by ALK fluorescence in situ hybridization (FISH) verification.@*Results@#There were 79 females and 88 males in the study cohort. The patient′s age ranged from 35 to 77 years (mean 62 years). Cases with solid growth pattern (at least >10%) and without typical histological features of adenocarcinoma, squamous cell carcinoma or neuroendocrine carcinoma were further divided based on immunohistochemistry and mucin stain into 64 cases(38.32%)of adenocarcinoma, 34 cases(20.35%) squamous cell carcinoma, 21 cases(12.57%)large cell neuroendocrine carcinoma, 5 cases(2.99%)combined large cell neuroendocrine carcinoma, 2 cases(1.20%)adenosquamous carcinoma and 41 cases(24.55%)large cell carcinoma. The Ki-67 positive rate ranged from 5% to 65%. Mutations of EGFR were detected in 5 cases (2.99%, 5/167) of adenocarcinoma(19del in 3 cases and L858R in 2 cases). Two cases(1.20%, 2/167) with ALK-rearranged were identified by immunohistochemistry (Ventana D5F3) and confirmed by ALK FISH.@*Conclusions@#Poorly differentiated solid lung cancer without distinct morphological features can be further histologically subtyped by mucin staining and immunohistochemistry. Molecular testing should be performed for accurate molecular target therapy to improve the prognosis.
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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.
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Objective To summarize the prevalence of diseases and main causes of death in elderly patients aged 80 and over,and to provide epidemiological evidence for preventive care of geriatric diseases.Methods A total of 922 autopsy cases aged from 60 to 106 at our hospital from April 1,1969 to October 31,2013 were analyzed.The disease spectrum and the main causes of death in cases aged 80 and over were compared with those in cases aged from 60 to 79.Results The top fifteen pathological diagnoscs in elderly patients aged 80 and over were chronic pyelonephritis(62.2 ％,290 cases),coronary heart disease(59.2％,276 cases),bronchopneumonia(52.6％,245 cases),prostatic hyperplasia (58.1％,232/399),pleural effusion (47.9％,223 cases),malignant tumor (47.4 ％,221 cases),chronic bronchitis(43.1 ％,201 cases),pulmonary congestion or edema(42.1 ％,196 cases),pericardial effusion (41.8 ％,195 cases),old myocardial infarction (40.1 ％,187 cases),emphysema (36.3％,169 cases),chronic cystitis (22.7％,106 cases),gallstones or cholecystitis (14.2％,66 cases),acute myocardial infarction (13.7％,64 cases),and gastrointestinal bleeding (12.4 ％,58 cases).The leading causes of death were malignant tumor (47.4 ％,221 cases),infectious disease(26.6％,124 cases)with pneumonia as the most prevalent type(24.0％,112 cases),and cardiovascular disease (myocardial infraction and heart failure) (24.7％,115 cases).Conclusions The most prevalent diseases in patients aged 80 and over are chronic pyelonephritis,coronary heart disease,bronchopneumonia,and malignant tumor.The top three causes of death in the aged are malignant tumor,cardiovascular disease.and pneumonia.Enhanced screening and management of the above diseases for inpatients aged 80 and over are recommended.
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Objective To investigate the histopathological characteristics of metastatic castration-resistant prostate cancer.Methods Clinical findings,morphologic features,immunophenotypes of androgen receptor (AR),prostatic specific antigen (PSA),chromogranin A (CgA),and phosphatase and tensin homolog deleted on chromosome ten(PTEN)(by EnVision method) of 178 core biopsies from patients with metastatic castration resistant prostate cancer encountered from January 2010 to January 2015 from West Coast Dream Team were analyzed.Results In the 178 cases,51(28.7％)were diagnosed with typical adenocarcinoma,41 cases(23.0％)with intermediate atypical carcinoma and 24 cases(13.5 ％)with small cell carcinoma.The expression of PSA was significantly lower in patients with intermediate atypical carcinoma or with small cell carcinoma(31/39,79.5 ％) than in those with adenocarcinoma(20/20,100 ％).The expression of PTEN was significantly higher in patient with intermediate atypical carcinoma or with small cell carcinoma (31/46,67.4％) than in those with adenocarcinoma (19/41,46.3％).Conclusions Three histopathological subtypes exists in metastatic castration-resistant prostate cancer,including adenocarcinoma,intermediate type atypical carcinoma and small cell carcinoma.They are entities with unique pathological features.The expression of PTEN is significantly lower in the patients with intermediate atypical carcinoma or with small cell carcinoma than in those with adenocarcinoma,indicating that intermediate atypical carcinoma and small cell carcinoma are different from typical adenocarcinoma in tumor occurrence and progression.
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Objective To characterize autopsy pathological changes of the coronary artery and left ventricular myocardium in elderly patients with moderate to severe calcified aortic stenosis,and to analyze the causes of death.Methods Seventeen cases of moderate to severe calcified aortic stenosis were identified from an autopsy database of Beijing Hospital containing 909 elderly patients(aged from 60-100 years)collected from April 1,1969 to October 31,2013.All cases were confirmed by autopsy and were analyzed retrospectively.The characteristics of coronary artery lesions,myocardial pathological changes and causes of death were summarized.Results Aortic stenosis was detected in 1.1％(2/190),1.9％(5/266),3.7％(11/297)and 6.4％(10/156)of patients in the 60-69,70-79,80-89 and 90-100 age groups,increasingly prevalent with age(x2=10.08,P=0.018).In addition,seventeencases were confirmed to have moderate to severe calcified aortic stenosis.Of these cases,13 (76.5％) had coronary artery disease and 5 (29.4 ％)had severe coronary stenosis.The left anterior descending (LAD) artery was most commonly involved(47.0 ％).No thrombus was found in the coronary arteries,and only one had chronic total occlusion(5.9 ％).Myocardial infarction was confirmed in all 13 patients with coronary artery disease,including six cases(35.3％)of AMI,11 cases(64.7 ％)of OMI and four cases (23.5 ％)of AMI and OMI.Among AMI cases,transmural infarction was shown only in one case,with two cases of non-transmural infarction,two cases of subendocardial infarction and one case of focal myocardial infarction.Among OMI cases,transmural infarction was shown in one case,with two cases of non-transmural infarction,four cases of subendocardial infarction and four cases of focal myocardial infarction.The clinical misdiagnosis rate of OMI was as high as 81.8％.Patients died mainly from cardiovascular disease(70.6 ％),with six cases (35.3 ％) from myocardial infarction,three from heart failure(17.6％) and three from malignant arrhythmia (17.6 ％).Six of the cases suffered from sudden cardiac death(35.3％)with biopsy-confirmed myocardial infarction changes.Conclusions The incidence of CAD in elderly patients with calcific aortic stenosis is high.Pathological changes of myocardial infarction,especially of subendocardial and focal infarction,occur in patients with moderate to severe aortic stenosis and coronary heart disease with a high clinical misdiagnosis rate.Aortic stenosis implicates both the valve and myocardium.Assessment of myocardial lesions in patients with calcific aortic stenosis should be carefully conducted in clinical practice.
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Objective@#To analyze the pathological feathers of the heart in elderly (60-99 years old) heart failure patients with preserved ejection fraction (HFpEF) and coronary artery disease (CAD) and to explore the misdiagnosis and missed diagnosis rates.@*Method@#This retrospective study included 154 HFpEF (left ventricular ejection fraction (LVEF)≥50%) cases and 49 heart failure with reduced ejection fraction (HFrEF) (LVEF≤40%) cases aged 60-99 years old out of 1 485 consecutive autopsy cases. Pathological changes of the heart and coronary artery were compared between patients with HFpEF and HFrEF. The misdiagnosis and missed diagnosis rates of HFpEF were analyzed based on pathological examination.@*Results@#Patients with HFpEF were older than those with HFrEF ((85.7±7.4) vs. (82.9±7.8) years old, P=0.017). Among all the cases, CAD was diagnosed in 105 (68.2%) HFpEF patients and 38 (77.6%) HFrEF patients. Compared with patients with HFrEF, HFpEF patients displayed less acute myocardial infarction (12.3%(19/154) vs. 59.2%(29/49), P<0.01) and more chronic myocardial ischemia (18.2%(28/154) vs. 6.1%(3/49), P=0.041). 51.9% (80/154) HFpEF and 71.4% (35/49) HFrEF patients (P=0.017) displayed >50% left anterior descending artery stenosis. Prevalence of >75% coronary arterial stenosis (51% (25/49) vs. 20.1%(31/154), P<0.001) and more than one vessel lesions (55.1%(27/49) vs. 33.8%(52/154), P=0.008) were significantly higher in HFrEF patients than in HFpEF patients. The misdiagnosis rate of CAD in HFpEF was 63.3% (31/49). Among HFpEF, the missed diagnosis rate of acute myocardial infarction was 57.9% (11/19) and the missed diagnosis rate of old myocardial infarction was 57.7% (45/78).@*Conclusions@#CAD and chronic myocardial ischemia are common in elderly patients with HFpEF. Chronic myocardial ischemia may play an important role in the development of HFpEF of elderly CAD patients. Among HFpEF patients, the misdiagnosis rate of CAD and missed diagnosis rate of myocardial infarction are high, so the accurate evaluation of myocardial ischemia status is of great importance.
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Objective@#To analyze the cardiac pathological features of elderly coronary artery disease (CAD) patients (60 years and over) and evaluate the pathological features at autopsy and risk factors of patients with acute myocardial infarction (AMI).@*Methods@#Data from 471 elderly patients (aged from 60 to 100 years old) with CAD confirmed by autopsy hospitalized in our hospital from April 1969 to October 2013 were retrospectively reviewed. Patients were divided into 2 groups: AMI group(n=128) with AMI as the primary cause of death and the rest served as control group(n=343). The pathological features of coronary lesion and related risk factors of AMI were analyzed.@*Results@#In patients aged 60 and over with CAD, 48.8%(230/471) had severe coronary stenosis, 18.7%(88/471) had three-vessel disease, 71.8% cases (338/471) had left anterior descending artery(LAD)grade Ⅲ and over stenosis, 29.9% (141/471) had LAD grade Ⅳ stenosis, 25.9%(122/471) had left main coronary artery(LM) grade Ⅲ and over stenosis, 9.6%(45/471) had LM grade Ⅳ stenosis, 27.1%(128/471) had AMI. The first AMI accounts for 39.1%(50/128), and 60.9%(78/128) had both AMI and old MI. Compared with the control group, AMI group were younger ((77.1±11.6) years vs. (83.2±9.1) years, P<0.01), had more severe coronary artery stenosis lesion (77.3%(99/128) vs. 38.2%(131/343), P<0.01), higher coronary index which reflects the overall arteriosclerosis (9.9±2.8 vs. 8.0±2.5, P<0.01), more three-vessel disease (30.3%(43/128) vs. 13.7%(45/343), P<0.01), heavier heart weight ((447.8±90.6)g vs. (426.6±99.1)g, P<0.05), higher prevlence of pulmonary congestion or edema (57.8%(74/128) vs. 39.9%(137/343), P<0.01). Twenty-three cardiac ruptures (23/128, 18.0%) were observed in AMI group. Logistic regression analysis showed that grade Ⅳ LAD stenosis (OR=3.55, 95%CI 2.05-6.17, P<0.01), three-vessel disease(OR=2.47, 95%CI 1.30-4.67, P<0.01) were the independent risk factors of AMI in elderly patients with CAD.@*Conclusions@#Severe coronary stenosis is common in CAD patients aged 60 and over. Patients aged 60 and over with AMI have more severe coronary artery stenosis lesion and heavier heart weight. Cardiac rupture is not uncommon in elderly patients with AMI. Severe LAD stenosis and three-vessel disease are the independent risk factors of AMI in the elderly.
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Objective@#To study the cytomorphologic features and determine whether pancreatic neuroendocrine tumors (PanNET) sampled by fine-needle aspiration (FNA) can be accurately graded based on the Ki-67 index when compared to surgical samples.@*Methods@#Corresponding intraoperative (19 cases) or endoscopic ultrasound-guided (3 cases) FNA cytology and surgical tissue specimens were obtained from 22 tumors, which were reviewed and stained for Ki-67 proliferation marker. The cytological samples included more than 200 tumor cells. Samples were graded by scoring the Ki-67 positive index in accordance with the 2010 WHO criteria. The grading scores assigned to the FNA cytology samples were compared with the scores assigned to the corresponding histological samples. Concordance was achieved by using 5% (instead of 2%) as a cut-off value for defining G2 tumors. One cytological sample included less than 500 tumor cells was excluded in the concordance calculation.@*Results@#The cytological smears consisted of uniform, monotonous and isolated cells, loose cellular aggregates and rosette-like formations. Some tumor cells clustered around segments of capillaries. The cells demonstrated distinct cytoplasmic and nuclear features. Mitoses and necrosis were rarely seen. When traditional 2% Ki-67 index cut-off value were used to classify G2 tumors, the majority (86.4%, κ=0.812, P<0.01) of FNA cytology samples and corresponding surgical tissue specimens demonstrated concordance. When a 5% cut-off value was adopted, the concordance rate was 95.5% (21/22, κ=1.000, P<0.01). Similar concordance rates between the cytological and histological grades were achieved with threshold value of cytological assessment material set at more than 500 or 200 cells.@*Conclusions@#The cytological Ki-67 index in adequate material (>200 tumor cells) is useful in grading pancreatic neuroendocrine tumors, and a cut-off value of 5% showed better predictive value compared with that of 2%. Accurate grading of PanNET is critical for predicting tumor biology, patient prognosis, and making informed decisions regarding patient management and treatment.
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The cell origin of primary pulmonary mucinous epithelial tumors includes goblet cells, tracheobronchial mucous glands, the mucous cell metaplasia of ciliated and Clara cells, etc.There are benign, low-grade malignant potential and malignant tumors in this category. The benign tumors encompass mucous gland adenoma and mucinous cystadenoma. Ciliated muconodular papillary tumors are thought to be of low grade malignant potential or uncertain malignant potential neoplasm, while colloid adenocarcinoma and mucinous adenocarcinoma are malignant tumors. Most of primary pulmonary mucinous epithelial tumors are rare even extremely rare lesions. Similar morphological changes exist in the different tumors. Differential diagnosis for these entities may be challenging in pathological diagnosis on biopsies, even surgical sections. The clinicopathologic characteristics should be carefully analyzed to ensure accurate pathologic diagnosis for primary pulmonary mucinous epithelial tumors.
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Cytology in China developed from nothing and underwent a long journey from gynecologic cytology to that of all organs, laying a solid foundation for new developments in the 21st century. Thyroid fine-needle aspiration (FNA) was primarily developed in an endocrinology department and then in the clinical laboratory department or pathology department in the 1970–80s. Wrights staining is popular in endocrine and clinical laboratory departments, while hematoxylin and eosin staining is common in pathology. Liquid based cytology is not common in thyroid FNA cytology, while BRAF(V600E) mutation analysis has been the most popular molecular test. The history and practice of thyroid FNA practice in China were reviewed based on retrospective study of the practice in Qilu Hospital of Shandong University.
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Biopsy, Fine-Needle , China , Endocrinology , Eosine Yellowish-(YS) , Hematoxylin , Pathology , Retrospective Studies , Thyroid GlandABSTRACT
<p><b>OBJECTIVE</b>The aim of this study was to establish a standardized protocol for detection of ALK protein expression and gene fusion in cytologic specimens.</p><p><b>METHODS</b>Lung adenocarcinoma cytologic specimens were collected from seven hospitals in Beijing city. A detection protocol for ALK protein expression and gene fusion was designed according to the results of comparative experiment. Ventana immunohistochemical (IHC) ALK(D5F3) detecting ALK protein expression was performed in 203 prepared formalin-fixed paraffin-embedded (FFPE) cell blocks. ALK gene fusion in 98 EGFR gene wild type cytologic specimens and in 4 bronchoalveolar lavage fluid (BL) samples was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). ALK gene fusion in the Ventana IHC ALK (D5F3) positive samples was further tested by fluorescence in situ hybridization (FISH). Six patients with ALK IHC-positive result were followed up to analyze the responses of crizotinib therapy. Comparative experiments: (1) Comparison of the results of 4% neutral buffered formalin fixed for different time (24 h, 48 h, 72 h) on the Ventana IHC ALK (D5F3) staining was conducted in two cases of IHC ALK positive FFPE cell blocks; (2) Comparing qRT-PCR results for ALK fusion in samples from FFPE cell blocks and cytospin prepared slides in 10 cases of lung adenocarcinoma cytologic specimens.</p><p><b>RESULTS</b>Among the specimens examined using the standardized protocol recommended by this study, 229 cases of cytologic specimens met the diagnostic criteria of lung adenocarcinoma. Among them, 207 cases obtained ALK gene test results (by at least one method), with an ALK test ratio of 90.4% (207/229). FFPE cell blocks were successfully prepared in 203 cases, Ventana IHC ALK (D5F3) were successfully performed in all the 203 FFPE cell blocks (100%), and the ALK protein positive detection rate was 10.3% (21/203). ALK fusion was tested in 98 FFPE cytologic samples of EGFR wild types by qRT-PCR, and 96 out of 98 (97.96%) cytologic samples were successfully performed.18 out of 19 IHC ALK-positive cases were verified to be of ALK fusion status by qRT-PCR. The concordance rate was 94.7% (Kappa=0.967, P<0.001) between Ventana IHC ALK (D5F3) and qRT-PCR, and the sensitivity of the Ventana IHC ALK (D5F3) assay compared with qRT-PCR was 100% and the specificity was 98.7%. FISH assay was used to verify the positive cases detected by Ventana IHC ALK (D5F3) staining. Two cases of low tumor cell content FFPE samples obtained indefinite results by FISH test. The six patients with positive ALK protein expression received crizotinib therapy, and 5 paitents got treated effectively. For two ALK IHC positive cases, which were 4% neutral buffered formalin fixed for 72 h, the result of Ventana IHC ALK (D5F3) staining became weakened obviously and uneven. In 10 cases of samples, total RNA was extracted from FFPE cytologic sections and cytospin prepared slides, and the results of qRT-PCR test and ALK gene fusion showed good concordance.</p><p><b>CONCLUSIONS</b>The standardized protocol recommended in this study expands the detection types and quantity of cytologic specimens for ALK protein expression and gene fusion and increased the detection rate. Ventana IHC ALK (D5F3) is a reliable method for detecting ALK protein expression in FFPE cell blocks. The pathologic quality control procedure prior to Ventana IHC ALK (D5F3) is crucial for the accuracy of testing the ALK gene status. When FFPE cell blocks could not be prepared or prepared unsuccessfully from the cytologic specimens, qRT-PCR may be an alternative option for the detection of ALK gene fusion.</p>