Abstract:Objective This study aims to analyze the diagnostic value of the combined detection of serum carbohydrate antigen 153(CA153),squamous cell carcinoma antigen(SCC),neuron-specific enolase(NSE),and cytokeratin 19 soluble fragment(CYFRA21-1)for lung cancer,as well as the association between these markers and the pathological classification of lung cancer.Methods From January 2019 to August 2021,112 patients with solitary pulmonary nodules in our hospital were enrolled.Fasting serum samples were collected to determine the levels of the above four indicators.Using pathological diagnosis by needle biopsy as the gold standard,the diagnostic efficacy(sensitivity,specificity,accuracy,positive predictive value,negative predictive value)of single-index detection and combined detection were compared.The differences in indicators between patients with lung cancer and benign pulmonary lesions were analyzed,the expression patterns of indicators under different pathological classifications,clinical stages,and lymph node metastasis statuses were explored,and the correlation between marker levels and pathological characteristics of lung cancer was clarified through correlation analysis.Results Among the 112 patients,72 were pathologically diagnosed with lung cancer(25 with small-cell lung cancer and 47 with non-small-cell lung cancer),and 40 with benign nodules;43 were in clinical stage Ⅰ-Ⅱand 29 in stage Ⅲ-Ⅳ;24 had lymph node metastasis and 48 had no metastasis.All indicators of diagnostic efficacy of the combined detection(sensitivity 97.22%,specificity 97.50%,accuracy 97.32%,positive predictive value 98.59%,negative predictive value 95.12%)were superior to those of single-index detection(P<0.05).The levels of the four serum indicators in lung cancer patients were higher than those in patients with benign pulmonary lesions(P<0.05);the indicator levels in patients with small-cell lung cancer were higher than those in patients with non-small-cell lung cancer(P<0.05);the indicator levels in patients with stage Ⅲ-Ⅳ were higher than those in patients with stage Ⅰ-Ⅱ(P<0.05);the indicator levels in patients with lymph node metastasis were higher than those in lung cancer patients without metastasis(P<0.05).Correlation analysis showed that the levels of the four indicators were positively correlated with the pathological classification,clinical stage,and lymph node metastasis of lung cancer(P<0.05).Conclusion The combined detection of CA153,SCC,NSE,and CYFRA21-1 can efficiently diagnose lung cancer,and can assist in distinguishing the pathological classification and clinical stage of lung cancer.Their expression levels are closely related to the pathological characteristics of lung cancer.

Abstract:Objective To investigate the clinicopathologic features and immunohistochemical characteristics of gastric SMARCA4-deficient undifferentiated carcinoma,in order to improve the understanding of the disease and to avoid underdiagnosis and misdiagnosis.Methods Five cases of gastric SMARCA4-deficient undifferentiated carcinoma diagnosed in the Department of Pathology,Provincial Hospital of Shandong First Medical University from September 2022 to February 2025 were collected,and their clinical data,pathological features,immunohistochemical staining results and follow-up were analyzed and summarized.Results The five patients were all elderly men,with the age of onset ranging from 59 to 73 years,and the median age was 68 years.The clinical symptoms were mainly abdominal discomfort,some of which were accompanied by abdominal distension,belching or abdominal pain.Pathological examination showed that the tumors occurred in different parts of the stomach,and were generally protruded or ulcerative masses with a maximum diameter of 4～6 cm,and the tumor cells were of various morphologies and obvious heterogeneity under the microscope,and some of them showed transverse muscle-like changes.Immunostaining staining results exhibited loss of BRG-1 expression,INI-1 was diffusely positive,mismatch repair proteins were positive(pMMR);neuroendocrine marker synaptophysin demonstrated focally weak positivity and CgA was negative;the Ki-67 proliferation index was 70%～90%;P53 staining results were diverse;HER2 staining was 0-1+in 3 cases,and 2+in 2 cases.In situ hybridization for EBER was all negative.2 patients underwent postoperative chemotherapy or a combination of chemotherapy plus immunotherapy and were followed up for 1-28 months,and all cases were still alive.Conclusion Gastric SMARCA4-deficient undifferentiated carcinoma is rare,with diverse histomorphological patterns,and the diagnosis needs to be combined with immunohistochemistry.Clinicians should improve their knowledge of this disease to avoid misdiagnosis and missed diagnosis.

Abstract:Objective To investigate the value of cell block combined with SRY-box transcription factor 17(SOX17)immunohistochemical detection in the diagnosis and differential diagnosis of metastatic gynecological carcinoma.Methods The cytological specimens of 84 cases of metastatic gynecologic carcinoma were collected,including 31 cases of peritoneal effusion,28 cases of pleural effusion,1 case of peritoneal flush fluid and 24 cases of fine needle aspiration.Among them,27 cases were metastatic gynecologic carcinoma(16 ovarian high-grade serous carcinomas,1 ovarian low-grade serous carcinoma,3 ovarian clear cell carcinomas,1 endometrioid carcinoma,1 uterine clear cell carcinoma,2 fallopian tube high-grade serous carcinomas,2 cervical mucinous adenocarcinomas and 1 cervical squamous cell carcinoma),and 57 cases were metastatic non-gynecological carcinoma(10 renal cell carcinomas,15 papillary thyroid carcinomas,2 gastric adenocarcinomas,2 colorectal adenocarcinomas,5 breast invasive carcinomas of no special type,1 pancreatic ductal adenocarcinoma,1 hepatic cholangiocarcinoma,19 lung adenocarcinomas,1 lung squamous cell carcinoma,and 1 esophageal squamous cell carcinoma).The above specimens were prepared with cell blocks,and SOX17 and PAX-8 was immunohistochemically detected.Meanwhile,the staining intensity and positive rate of tumor cells were evaluated.Results SOX17 was strongly nuclear diffuse positive in 24 metastatic gynecological carcinomas,and negative in 1 case of metastatic cervical squamous cell carcinoma in pleural effusion and 2 cases of metastatic cervical mucinous adenocarcinoma in peritoneal effusion.SOX17 was negative in 56 cases of non-gynecological metastatic carcinoma and focally positive in 1 case of metastatic pancreatic ductal carcinoma in pleural effusion.The sensitivity and specificity of SOX17 were 88.9%and 98.2%respectively in metastatic gynecological carcinoma.Conclusion SOX17 has high sensitivity and specificity in the diagnosis of metastatic gynecologic carcinoma,and SOX17 immunohistochemical detection is valuable for the diagnosis and differential diagnosis of metastatic gynecologic carcinologic specimens.

Abstract:Objective To explore the morphological characteristics of mesothelioma in situ(MIS)and to improve the morphological understanding of such lesions.Methods Clinical data of one MIS patient were collected,and the morphological features were retrospectively analyzed by effusion cytology,tissue biopsy,immunohistochemical staining and FISH detection,and the literature was reviewed.Results Significant morphological differences were observed between histological biopsy and hydropleural cytology.The histological morphology appeared benign and mild with consistent cell size,while the cytological morphology showed marked atypia,with large and hyperchromatic nuclei.By immunohistochemistry,they all showed positive expression of D2-40,CK5/6,Calretinin and CK,negative expression of TTF-1,and some weak expression of BAP-1.Both CDKN2A/P16 FISH assays were homozygous deletions.Based on the clinical presentation,imaging findings,and thoracoscopic examination results,the diagnosis was consistent with MIS.Conclusion MIS can exhibit morphological differences between serous effusions and tissue biopsy and the diagnosis should be comprehensively evaluated by combination with the clinical presentation,pathological morphology,immunohistochemistry,and related genetic testing results.

Abstract:Colorectal cancer(CRC)is one of the malignant tumors with high morbidity and mortality worldwide.In recent years,tumor budding,as an important biological feature of CRC,has gradually received attention from researchers.Tumor budding not only affects the invasiveness and metastatic ability of the tumor,but also is closely related to the prognosis of patients.Despite the current progress in the study of tumor budding,its specific biological mechanisms and complex interactions with the tumor microenvironment still need to be explored in depth.In this paper,we review the latest research progress of CRC tumor budding,including its biological mechanism,clinical significance,application of new emerging technologies in tumor budding,and future research directions,aiming to provide new ideas and methods to improve the prognosis of CRC patients and enhance their survival rate.

Abstract:Objective To analyze the clinicopathological characteristics,diagnostic criteria,and differential diagnosis strategies of multilocular cystic renal neoplasm of low malignant potential(MCRNLMP).Methods A retrospective analysis of clinicopathological features and immunophenotypes was conducted in 6 cases of MCRNLMP,supplemented by a review of relevant literature.Results Among the 6 MCRNLMP cases,the patients'ages ranged from 35 to 65 years(mean age:50.17±10.89 years),and tumor diameters ranged from 6 to 8 cm(mean diameter:6.50±0.84 cm).Gross examination revealed well-circumscribed multilocular cystic masses containing small amounts of pale yellow or dark brown fluid.Microscopically,the tumors were cystic,lined by a single layer of clear cells with occasional stratified epithelium and minimal nuclear atypia.Immunophenotypically,all 6 cases showed variable expression of PAX-8,carbonic anhydrase IX(CAIX),EMA,CK7,and CD10,while CD68 and CD117 were negative.The Ki-67 proliferation index ranged from 1%to 3%.During follow-up(16-42 months),no recurrence or metastasis was observed.Conclusion MCRNLMP is a rare renal tumor with favorable prognosis.Preoperative diagnosis is challenging,and definitive diagnosis relies on postoperative pathology.It must be differentiated from cystic renal cell carcinoma and benign renal cystic lesions,with immunohistochemical staining aiding in differential diagnosis.

Abstract:Objective To investigated the clinicopathological,immunophenotypes,molecular features and differential diagnosis of round cell sarcoma with EWSR1::PATZ1 fusions(EWSR1-non-ETS fusions).Methods We retrospectively analysed the clinical data,pathomorphology,immunophenotype and molecular of one EWSR1::PATZ1 sarcomas case diagnosed at the Department of Pathology,KingMed Diagnostics in 2023.The related literature was also reviewed.Results The patient was an 11-year-old boy with a solid mass of approximately 3.0 cm×1.5 cm×1.0 cm in the left parietal-occipital region of the skull.Microscopically,the tumor was diffuse oval or short spindle cell with solid papillary patterns.The tumor cells had abundant eosinophilic or clear cytoplasm,irregular nuclear membranes,frequent mitoses,focal necrosis,and hyaline degeneration of the interstitial blood vessels.Immunohistochemically,the tumor cells showed weakly positive for CD99,negative for DES,CgA,GFAP,PCK,S-100,ERG,with high Ki67 index reaching 60%.Fluorescence in situ hybridization(FISH)identified EWSR1 gene rearrangement.Next-generation sequencing(NGS)detected EWSR1::PATZ1 fusions and TP53 p.Y103* inactivation mutation.The patient was treated with CAV/IE chemotherapy regimen after surgery and was followed up for 19 months without disease recurrence.Conclusion Round cell sarcoma with EWSR1::PATZ1 fusions is a newly named rare sarcoma with a wide range of age,diverse morphology and immunophenotype.It needs to be differentiated from a variety of tumors.Detection of the EWSR1::PATZ1 fusion is the gold standard for diagnosis.There is no standard treatment and the prognosis is relatively poor.

Abstract:Objective To observe the clinical and pathological characteristics of inborn error of immunity-associated lymphoid proliferations diseases and lymphomas(IEI-LPD/L)with haemophagocytic lymphohistiocytosis(HLH).Methods A total of 22 patients of IEI-LPD/L with HLH were collected,and their clinical and pathological characteristics and related genetic defects analyzed.Results Among the 22 patients,there were 17 males and 5 females.The age ranged from 5 months to 58 years.In addition to the diagnostic clinical manifestations of HLH,there are also other manifestations,including lymph node enlargement(13 cases),multiple serous fluid accumulation(3 cases),multiple dermatitis(2 cases),mumps(1 case),central nervous system symptoms(5 cases).Pathologically,different pathological features were displayed due to different sampling sites,including classic Hodgkin lymphoma,angioimmunoblastic T-cell lymphoma,EBV+lymphoproliferative diseases,dermatitis,mumps,lymph node reactive hyperplasia,and hemophagosis of bone marrow.Characteristics of EBV infection showed that among the 22 patients,19 had blood tests showing EBV infection;18 patients showed EBV infection in different tissue biopsies,of which 8 tissues showed EBNA2 positive.The detected genetic abnormalities and related immune syndromes mainly included:six cases of UNC13D gene abnormalities;four cases of PRF1 gene abnormalities;three cases of SH2D1A gene abnormalities;three cases of MAGT1 gene abnormality;two cases of GATA2 gene abnormalities;one case of MKL1 gene abnormality;one case of WASP gene abnormality,and one case of UBA1 gene abnormality.Follow-up showed that twelve patients underwent bone marrow transplantation,of which one developed CNS symptoms after transplantation,two were waiting for transplantation,three died,and three received symptomatic treatment and follow-up.Conclusion HLH and IEI-LPD/L are clinical names,and their pathological manifestations can be diverse,including tumor or non-neoplastic changes;Young people with EBV infection(especially multi lineage infection)and positive EBNA2 indicate the presence of immune dysfunction or genetic defects.

Abstract:Objective To investigate the prognostic value of microtubule depolymerisation protein 1(Stathmin 1,STMN1)in hepatocellular carcinoma(HCC)and its impact on immunotherapy response.Methods Integrate databases such as TCGA,GTEx,and CPTAC,combining single-cell and spatial transcriptomics data were used to analyze the expression characteristics of STMN1 in HCC;the association between STMN1 expression and patient prognosis were evaluated in HCC using forest plots,Kaplan-Meier curves,and ROC analysis;its prognostic value for HCC was determined through univariate and multivariate Cox regression.Stromal scores and the TIMER database were utilized to elucidate the relationship between STMN1 and the immune microenvironment of HCC;the TIDE algorithm was used to predict the impact of STMN1 expression on the therapeutic response to immune checkpoint inhibitors(ICIs).STMN1 expression was detected in 100 cases of HCC and normal tissues via immunohistochemical staining to analyze its correlation with clinical pathological features of HCC patients.Results Comprehensive analysis found that STMN1 was highly expressed in HCC tissues;High expression of STMN1 was closely related to poorer prognosis and could serve as an independent prognostic factor for HCC.STMN1 expression was negatively correlated with the stromal score but positively correlated with various immune cells and regulatory genes.The response rate to immunotherapy was significantly higher in the low STMN1 expression group than that in the high STMN1 expression group.Immunohistochemical results confirmed that STMN1 was highly expressed in HCC tissues,which was significantly associated with moderately differentiated tumor and diameter in HCC(P<0.05),but not significantly correlated with gender and age(P>0.05).Conclusion STMN1 is a valuable biomarker for predicting the prognosis and immune therapy response of HCC,which can provide new directions for the prognosis and treatment of HCC.

Abstract:Objective To explore the clinicopathological features,diagnosis and differential diagnosis of fibroblastic reticular cell tumor(FRCT).Methods A case of orbital FRCT was retrospectively analyzed and relevant literature was reviewed.Results The patient underwent resection and biopsy of a right orbital mass.Microscopically,the mass showed nodular growth,with spindle tumor cells arranged in bundles,whorls and storiform patterns.A few small lymphocytes were seen infiltrating between the spindle tumor cells,and scattered lymphoid follicular structures were present in some areas.The boundaries of the spindle tumor cells were unclear,and the cytoplasm was pale eosinophilic.The short spindle or oval vacuolated nuclei showed mild atypia,with smooth or slightly irregular nuclear membranes.Small nucleoli were seen in some nuclei,but mitosis was rare.The spindle tumor cells were positive for CD68,Bcl-2,and Bcl-6,partially positive for S100 and EMA,and weakly positive for Desmin;while PCK,LCA,CD1α,CD3,CD5,CD10,CD20,CD21,CD23,CD35,CD79α,Caldesmon,C-myc,CyclinD1,D2-40,and SMA were all negative.The positive rate of Ki-67 was approximately 5%.Conclusion FRCT is a rare low-grade malignant tumor of fibroblastic reticular cell origin,mostly occurring in lymph nodes,and is extremely rare in the orbit.The pathological diagnosis mainly relies on histomorphology and immunophenotype,and it needs to be differentiated from many other tumors.

Abstract:Objective To investigate the differential significance of BRAF,TERT,KRAS,NRAS,and HRAS genes in the preoperative risk stratification system for thyroid follicular-derived nodules.Methods A total of 112 patients with thyroid nodules meeting the inclusion criteria were selected.All patients underwent preoperative fine-needle aspiration cytology(FNAC)and genetic testing(covering 5 gene loci:BRAF,TERT,KRAS,NRAS,and HRAS).Postoperative pathological diagnosis served as the"gold standard"to analyze the differential significance of these genes in risk stratification.Results Postoperative pathological diagnoses classified the 112 cases as benign tumors(63 cases),low-risk tumors(18 cases),and malignant tumors(31 cases).Clinicopathological information of thyroid follicular tumors across different risk levels showed no statistically significant differences in gender(P=0.05),age(P=0.712),FNAC site(P=0.200),or tumor size(P=0.615).However,cytological Bethesda classification(P=0.005),capsular invasion(P=0.001),and lymph node metastasis(P=0.001)exhibited statistically significant differences(P<0.05).Genetic testing results revealed no statistically significant differences in mutation rates of BRAF(P=0.198),KRAS(P=0.675),NRAS(P=0.209),HRAS(P=0.639),TERT(P=0.070),or RAS(P=0.058)among different risk-level groups.Conclusion In the risk stratification of thyroid follicular-derived nodules,mutations in BRAF,TERT,KRAS,NRAS,HRAS,and RAS genes do not demonstrate significant differential significance,whereas cytological Bethesda classification,capsular invasion,and lymph node metastasis show positive correlations with malignancy.

Abstract:Objective To explore the clinicopathological features,diagnosis,differential diagnosis,treatment and prognosis of congenital juvenile xanthogranuloma(JXG).Methods The clinical data of 8 cases of congenital JXG were collected.Hematoxylin-eosin(HE)staining and immunohistochemical EnVision two-step staining were used to analyze the clinicopathological features,and the relevant literature was reviewed.Results In this group,there were 6 male cases and 2 female.Seven cases presented with single red or yellow nodules on the skin,with a diameter ranging from 0.5 to 4.0 cm.One case had multiple small nodules with a diameter of 1.0-2.0 cm.Microscopic examination revealed diffusely proliferating mononuclear histiocytes.The cytoplasm was abundant and eosinophilic.Variable numbers of foam cells and Touton cells were observed,accompanied by infiltration of eosinophils and lymphocytes to varying degrees.Immunohistochemical staining showed that the tumor cells were positive for CD68 and CD163,but negative for S-100,Langerin,CD1a,and ALK.The pathological diagnosis was juvenile xanthogranuloma.Conclusion Congenital juvenile xanthogranuloma is relatively rare.Microscopically,it is characterized by histiocyte proliferation with varying numbers of Touton cells.Familiarity with the clinicopathological features of this disease can avoid misdiagnosis and overtreatment.

Abstract:Objective To explore the clinicopathological features and immunophenotypes of angiomatoid fibrous histiocytoma(AFH),aimed to provide a basis for its diagnosis and differential diagnosis.Methods The clinical and pathological data of four cases of AFH at Northern Jiangsu People's Hospital from 2012 to 2024 were retrospectively analyzed.Relevant literatures were reviewed.Results Pathologically,the tumor had a clear boundary,with surrounding lymphoid tissue visible.Tumor cells were arranged in nodular or nest-like patterns,and the tumor contained irregular hemorrhagic cystic cavities.Immunohistochemically,the tumour cells were positive for EMA,CD99,and Desmin.Fluorescence in situ hybridization(FISH)detection confirmed the presence of EWSRl gene split signals in all 4 cases.Conclusion AFH is a rare intermediate soft tissue tumor.Accurate diagnosis can be achieved by combining histopathological findings with related examinations,which provides a basis for clinical treatment.

Abstract:Objective To investigate the clinicopathological features,immunophenotypic characteristics,molecular alterations,diagnosis,and differential diagnosis of Napsin A-positive thyroid carcinoma(TC).Methods The clinical manifestations,histopathological features,immune/molecular phenotypes and differential diagnosis of Napsin A-positive TC were retrospectively analyzed,and the relevant literature was reviewed and discussed.Results There were 2 females and 4 males,with an average age of 49 years(range,28-67 years).Among them,cervical lymph node puncture biopsy was performed in 3 patients,cervical lymph node excision biopsy was performed in 1 patient,percutaneous lung puncture biopsy was performed in 1 patient,and axillary lymph node puncture biopsy was performed in 1 patient.Histologically,there were 4 cases of micropapillary/hobnail variant of papillary thyroid carcinoma(PTC),1 case of poorly differentiated thyroid carcinoma,and 1 case of classical variant of PTC with micropapillary/hobnail components.Immunohistochemical results showed that PAX-8,Tg,TTF-1,CK7 and CK19 were all positive in 6 patients.Napsin A was positive,with varying staining intensities.Molecular testing revealed TERT promoter mutations.Conclusion The NapsinA-positive metastatic thyroid carcinoma is typically a more aggressive special histological subtype with molecular alterations indicating a poor prognosis.It needs to be differentiated from the NapsinA-positive metastatic lung adenocarcinoma.The positive expression of PAX-8 is critical for the differentiation between the two tumors.

Abstract:Objective To investigate the expression of interleukin-28 receptor α(IL28RA)in esophageal carcinoma and its clinical significance.Methods Clinical data of 146 patients who underwent radical resection for esophageal carcinoma from April 2015 to May 2020 were retrospectively analyzed,with a 3-year postoperative follow-up.The expression of IL28RA in cancer tissues and adjacent tissues of all patients was detected.The correlation of IL28RA expression with clinicopathological characteristics,postoperative recurrence,and metastasis was analyzed.Results The positive expression rate of IL28RA protein in cancer tissues was lower than that in adjacent tissues(P＜0.05).The positive expression rate of IL28RA protein was lower in poorly differentiation,stage Ⅲ,and lymph node metastatic cancer tissues than in moderately/well-differentiated,stage Ⅱ,and no lymph node metastatic cancer tissues(P＜0.05).Cox regression analysis showed that pathological stage(RR=6.482,95CI％:2.667-15.753),differentiation degree(RR=4.968,95％CI:2.044-12.074),and positive IL28RA protein expression(RR=0.409,95CI％:0.168-00.994)were factors affecting postoperative recurrence and metastasis in patients with esophageal cancer(P＜0.05).The disease-free survival of patients with positive expression of IL28RA protein was better than that of patients with negative expression(P＜0.05).Conclusion IL28RA is lowly expressed in esophageal cancer tissues.Patients with positive IL28RA protein have a lower risk of postoperative recurrence and metastasis.

Abstract:Objective To investigate the histopathological features,immunophenotype,differential diagnosis,molecular subtypes,and genetic variation characteristics of corded and hyalinized endometrioid carcinoma(CHEC).Methods The clinicopathological data of 5 cases of CHEC were retrospectively analyzed,supplemented by immunohistochemical staining and molecular pathological detection.A systematic review of relevant literature was conducted.Results The cohort had a mean age of 36 years,with tumors classified as FIGO stage IA(n=1),IB(n=2),and Ⅲ A(n=2).The mean follow-up time was 16 months,with all patients remaining disease-free.Histologically,tumors exhibited a biphasic morphology:conventional endometrioid carcinoma intermingled with infiltrative epithelioid-to-spindled cells embedded in hyalinized stroma.Tumor cells demonstrated mild-to-moderate nuclear atypia,with low proliferative activity(mean mitotic count:1.6/10 HPF;wild-type p53 expression;low Ki-67 proliferation index).Molecular subtyping revealed that the majority were of the NSMP type(4/5,80％),and one case was of the p53-mutant type(1/5,20％).Common genetic mutations included CTNNB1(4/4),ARID1A(3/4),PTEN(3/4),and PIK3CA(2/4).Conclusion CHEC represents a distinct and rare subtype of endometrioid carcinoma,and TCGA-based subtyping has important clinical value in this tumor.High-frequency CTNNB1 mutation is one of its characteristics and serves as a high-risk stratification factor in the NSMP subtype.