Purpose To investigate the incidence and risk of malignancy(ROM)of the Bethesda class Ⅰ/Ⅲ di-agnosis of thyroid nodules due to insufficient number of follicular cells,and to analyze the correlation between their in-sufficient cell volume and the characteristics of the nodules themselves from the perspective of ultrasound and histology.Methods Clinical data were collected from fine needle aspiration cytology(FNAC)of the thyroid gland.Review and statistical analysis was performed on cases with the Bethesda class Ⅰ/Ⅲ diagnosis due to insufficient cell volume.The incidence and the ROM of Bethesda class Ⅰ/Ⅲ diagnosis were calculated.BRAF V600E(+)or postoperative patho-logical indicating papillary thyroid carcinoma(PTC)was used as the criterion for malignancy.Then,we matched the Bethesda class Ⅱ/Ⅵ cases with sufficient cell volume as the control group.The ultrasound characteristics and histo-logical images of the two groups were compared and analyzed in order to reveal the correlation between the insufficient amount of penetrating cells and the objective characteristics of the nodule itself.Results There were 39 solid thyroid nodules with the Bethesda class Ⅰ diagnosis,with an incidence of 3.3％and a ROM of 38.5％,and 160 nodules with the Bethesda class Ⅲ diagnosis,with an incidence of 13.5％and a ROM of 59.4％.The incidence and ROM of nod-ules with C-TIRADS ≥4b(22.4％,67.6％)were higher than those of C-TIRADS ≤4a(12.7％,39.8％),and the differences were statistically significant(P＜0.001).Compared to the Bethesda class Ⅱ/Ⅵ nodules with sufficient cell volume,occurrence of the Bethesda class Ⅰ/Ⅲ nodules were significantly correlated with small nodules(maximal diameter＜5 mm),vertical growth(aspect ratio ≥ 1)and poor blood supply(no or little blood flow signals)(r=0.131,-0.230,0.237,P=0.008,＜0.001,＜0.001).They were also significantly correlated with the pathologic histologic structure of diffuse significant fibrosis of the interstitium and low parenchyma/interstitium composition ratio(about 1:1)(r=-0.269,-0.396,P=0.019,＜0.001).Conclusion Thyroid Bethesda class Ⅰ/Ⅲ nodules have a high ROM,and BRAF V600E detection is recommended as a tool of tiered management.Bethesda class Ⅰ/Ⅲ diagnosis of insufficient cell volume is more likely when the nodules are too small,grow vertically and lack blood sup-ply,presumably associated with extensive interstitial fibrosis and sparse parenchymal cells.

Purpose To investigate the clinicopathologic characteristics and prognostic factors of follicular thyroid carcinomas(FTC).Methods The clinical and pathological data of 205 FTC patients were collected,and the clinico-pathologic characteristics of FTC and its impact on prognosis were analyzed.Results The most common site of metas-tasis of FTC was bone(25.4％),which were mainly vertebrae and pelvis,followed by lung(15.6％).The factors that affecting distant metastasis(DM)were as follows:≥2 tumor foci,stage(Ⅲ-Ⅳ),patients'age(≥55 years,ex-tensive invasive type,recurrent FTC,postoperative/post-treatment recurrence and metastasis,and patients with com-plete tumor resection had less DM(P＜0.05,respectively).The factors that affecting the number of tumor foci includ-ed age,stage(Ⅲ-Ⅳ),extensive invasive type,recurrent FTC,distant metastasis and history of hypertension,more recurrence and metastasis after surgery/treatment(P＜0.05,respectively).Univariate survival analysis showed that factors affecting the overall survival(OS)and cancer-specific survival(CSS)of FTC were as follows:the number of tumor foci,stage,patients'age,surgical mode,extensive invasive type,DM,smoking,and postoperative/post-treat-ment recurrence.Cox multivariate regression analysis showed that stage,smoking and distant metastasis affected OS and/or CSS,and stage,extensive invasive type and recurrent FTC affected relapse-free survival(RFS).Compared with the group of FTC without undifferentiated carcinoma(UTC),the group of FTC with UTC had later stage(Ⅲ-Ⅳ,100.0％vs 32.0％),older age(≥ 60 years old,87.5％vs 37.6％),bigger size(＞4 cm,100.0％vs 44.2％),higher proportion of extensive infiltration type(100.0％vs 33.3％),shorter survival time[CSS(4.429±1.152)months vs(120.415±5.765)months,P＜0.001].Conclusion The most common site of distant metastasis of FTC is bone.Older patients,extensively invasive type and recurrent cancer are prone to multifocal and distant me-tastases.There were many prognostic factors affecting of FTC.The group of FTC with UTC has worse prognosis.

Purpose To investigate the clinicopathological features,diagnosis,differential diagnosis,treatment,and prognosis of intrathyroid thymic carcinoma(ITC).Methods The clinical manifestations,histological features and immunophenotypes of 11 patients with ITC were retrospectively analyzed.Immunohistochemistry and Sanger sequencing were used for protein and gene detection.The relevant literature is retrieved and the data of this paper is analyzed sta-tistically.Results Among the 11 patients,6 were female and 5 was male,aged from 35 to 75 years old.Tumor inva-sion into peripheral thyroid tissue was observed in 2 cases.Immunohistochemical analysis revealed positive expression for CD5,CD117,p63,p40,CK5/6,CK17 and CKpan,with focal positivity for Syn observed in only 1 case.Genetic testing:1 patient had mutations in the TERT promoter gene(C.-228 C＞T).Conclusion ITC is an extremely rare,low-grade malignant tumor.Due to its morphological similarity to other highly malignant thyroid tumors,it is prone to misdiagnosis.Immunohistochemistry and genetic testing play a crucial role in accurate differential diagnosis.

As an important parameter in the field of pathological morphology,tumor budding is the histological ba-sis for tumor invasion and metastasis,which is reflected in various types of cancer,such as oropharyngeal cancer,colo-rectal cancer,esophageal cancer,lung cancer,uterine cancer,etc.The in-depth study of tumor budding by scholars suggests that it can be used as a prognostic indicator for head and neck squamous cell carcinoma(HNSCC).This arti-cle aims to review the research progress on the occurrence,grading,and prediction of cancer prognosis in tumor bud-ding,with the hope of providing assistance in clinical treatment decision-making for HNSCC.

Purpose To compare the expression and pattern of EBNA2 in infectious mononucleosis(IM),EBV-positive diffuse large B-cell lymphoma(EBV+DLBCL),and EBV+DLBCL arising in immune deficiency/dysregulation(IDD-related EBV+DLBCL),and to investigate the potential diagnostic value of EBNA2 in IM and EBV-associated diffuse large B-cell lymphoma.Methods A retrospective study was conducted on 46 cases of IM,31 cases of EBV+DLBCL,and 16 cases of IDD(post-transplantation)-related EBV+DLBCL.Clinical information,immunohistochemis-try and EBER were reviewed to further confirm the diagnoses.All samples were stained for EBNA2.The expression ra-tio and intensity of EBER and EBNA2 in the same area were assessed.Results EBER was positive in all IM,EBV+DLBCL,and IDD(post-transplantation)-related EBV+DLBCL,while the positivity rate of EBNA2 was 95.65％,6.45％,and 100％,respectively.The positive intensity of EBNA2 was weak(71.73％),strong(87.5％)and nega-tive(93.54％)in IM,IDD(post-transplantation)-related EBV+DLBCL and EBV+DLBCL respectively.The average values of EBNA2/EBER were 31％,3％,and 78％among the three groups.The positivity rate and average value of EBNA2/EBER in IM were significantly higher than those in EBV+DLBCL(P＜0.001);however,the average value of EBNA2/EBER was significantly lower than that in IDD(post-transplantation)-related EBV+DLBCL(P＜0.001).The weak positive expression of EBNA2 in IM was significantly higher than that in EBV+DLBCL(P＜0.001),where-as strong positive expression of EBNA2 in IDD(post-transplantation)-related EBV+DLBCL was higher than that in IM(P＜0.001).Conclusion EBNA2 is often positive in IM and predominantly weakly positive,which is distinct from the pattern in EBV+DLBCL and IDD(post-transplantation)-related EBV+DLBCL.EBNA2 can serve as an effective marker for distinguishing them.

Purpose To explore the pathological characteristics,diagnosis,and differential diagnosis of pure ery-throid leukemia(PEL).Methods A retrospective analysis was conducted on the clinicopathological data of 12 cases of PEL.Immunohistochemical EnVision method and flow cytometry were used to detect PEL-related immune markers,and heat-treated Giemsa R-banding technique was applied to analyze the chromosomal karyotype.Results Peripheral blood and bone marrow smears revealed that 2 out of 7 cases showed presence of proerythroblast in peripheral blood,and 7 out of 12 cases showed atypical proerythroblast in bone marrow samples.After recounting,the average percentage of proerythroblast in the 12 PEL cases was 36.8％(ranging from 2％to 69.5％),with an average of 53.2％of all er-ythroid cells(ranging from 5％to 88％).Among them,9 cases did not meet the diagnostic criteria for PEL.Bone marrow biopsy:11 cases showed hypercellularity,with tumor cells showing diffuse proliferation in 9 cases,accompa-nied by dysplasia of megakaryocytes in 7 cases,and there was increased proliferation of fibrous tissue in 9 cases.Im-munohistochemistry:12 cases exhibited strong staining intensity for CD71 and E-cadherin.11 cases expressed CD117,while 4 cases expressed CD34,3 cases exhibited slight expression of GPA,and 1 case weakly expressed CD61.Flow cytometry:in 8 cases,there was an increased proportion of early-stage erythroid cells,accounting for 3.1％to 80.31％of nucleated cells,with an average of 31.0％.All cases expressed CD117 and CD71 to varying degrees,with 7 out of 8 cases expressing CD36,5 out of 7 cases expressing CD105,and 3 out of 4 cases expressing GPA.A few ca-ses demonstrated aberrant expression of CD123 and CD7.Chromosomal Karyotyping:7 cases exhibited highly complex karyotypes(7/8),with frequent involvement of chromosomes 5,7,8,17,and 19.One case had a normal karyotype.Conclusion The diagnosis of PEL requires a comprehensive assessment combining various methods including bone marrow smears,bone marrow biopsy,immunohistochemistry,and flow cytometry.

Purpose To explore the clinicopathological features,diagnosis and differential diagnosis of mantle cell lymphoma(MCL)with aberrant expression of CD10.Methods 14 cases of MCL with aberrant expression of CD10 were analyzed using hematoxylin-eosin,immunohistochemical stains,in situ hybridization,and fluorescence in situ hy-bridization(FISH)techniques to observe the histological morphology,immunophenotype,and molecular genetic char-acteristics.The relevant literatures were reviewed.Results There were 11 males and 3 females,with a male-to-fe-male ratio of 11∶3.The age ranged from 49 to 80 years,with an average age of 64.4 years and a median age of 64 years.10 cases occurred in lymph nodes,1 case in the nasopharynx,1 case in the right colon,1 case in the right eye-lid,and 1 case in the right testis.According to the Ann Arbor staging system,8 cases were classified as stage Ⅳ and 5 cases as stage Ⅲ,and 1 case with undetermined staging.Histologically,there was diffuse effacement of the normal architecture by tumor cells infiltration.Transparent degenerate small blood vessels and scattered individual epithelial-like tissue cells could be observed in the background.Among them,8 cases(8/14,57.14％)were composed of uni-form small to medium-sized lymphocytes with slightly irregular nuclei,unevenly dispersed chromatin,inconspicuous nucleoli,and scant cytoplasm,along with observable mitotic figures.In 3 cases(3/14,21.43％),the tumor cells were large and markedly pleomorphic,with round or irregular nuclei,prominent nucleoli,frequent mitotic figures,and abundant pale cytoplasm.Tumor cells in 3 cases(3/14,21.43％)were resembling lymphoblasts,characterized by round nuclei,fine chromatin,inconspicuous nucleoli,frequent mitotic figures,and scant cytoplasm.Immunophenotyp-ically,CD21 staining showed residual follicular dendritic meshworks.The tumor cells were diffusely and strongly posi-tive for CD20(14/14),PAX5(7/7),CD5(14/14),Cyclin D1(14/14),SOX11(11/11),and BCL2(13/13),partially positive for BCL6(8/14,57.14％)and MUM1(6/9,66.67％),but negative for CD3(14/14)and CD23(14/14).Among 14 cases,10 cases were diffusely and strongly positive for CD10(10/14,71.43％),and 4 cases were partially positive for CD10(4/14,28.57％).The percentage of Ki67 index ranged from 10％to 90％.All cases were negative for EBER(8/8).FISH analysis was performed in 9 cases,among which 7 cases showed CCND1 gene rearrangement,another 2 cases failed to detect due to insufficient tissue samples.Bone marrow biopsy was performed in 13 cases,revealing involvement in 8 cases(8/13,61.54％)and no involvement in 5 cases(5/13,38.46％).Con-clusion MCL with aberrant expression of CD10 is very rare,which commonly exhibits a diffuse growth pattern and blastoid and pleomorphic variants.It often has a high Ki67 proliferation index and poorer prognosis,and should be dis-tinguished from other subtypes of CD1O-positive B-cell lymphomas.

Purpose To investigate the clinicopathological features and prognostic factors of follicular dendritic cell carcinoma(FDCS).Methods Hospital records of 23 patients diagnosed with FDCS were retrospectively re-viewed.The morphological,immunohistochemical features,including the detection of CD21,CD23,and CD35 using the EnVision method,and in-situ hybridization for Epstein-Barr virus encoded nuclear RNA(EBER)were evaluated.Clinicopathological characteristics were analyzed for the evaluation of prognosis.Results The median age of all 23 pa-tients was 50 years(range:27 to 72)and the female to male ratio was 1.3.The median maximum diameter of tumor was 7.0 cm(range:0.5 to 20.0 cm).One case was located in cervical lymph node,while another 22 were discovered in extranodal sites.20 cases were single organ and 3 cases were multiple organs involvement.Microscopically,tumor cells exhibited spindle,oval,or markedly pleomorphic morphology,accompanied by variable lymphoplasmacytic infil-tration in the stroma.CD21,CD35 and CD23 were positive in 22 of 23(95.6％),23 of 23(100.0％)and 4 of 15(26.7％)patients,respectively.EBER in-situ hybridization was positive in 9 of 23 patients(39.1％).The median follow-up time was 84.0(95％CI:50.7-117.3)months,and the 5-year survival rate was 80.2％(95％CI:62.8-97.6).Twelve(52.2％)patients were alive,5(21.7％)were dead,and 6(26.1％)were lost of follow-up.We es-tablished a pathological scoring system containing 5 indexes,i.e.,tumor maximum diameter,mitotic figures,tumor necrosis,cellular pleomorphism and histologic types.Patients with greater than 4 points had a significant poor progno-sis.Conclusion FDCS features a broad spectrum of histologic appearances and behavior.Combined morphological observations(HE staining),applications of a panel of follicular dendritic cell markers and EBER in-situ hybridization are helpful for accurate diagnosis.FDCS poses risks for recurrence,metastasis and death,and those with greater than 4 points in the scoring system have a significant poor prognosis.Long-term follow up is needed.

Purpose To investigate the clinicopathological features,differential diagnosis and prognosis of atypical fibroxanthoma(AFX).Methods Pathological features of 15 cases of AFX and 3 cases of pleomorphic dermal sarcoma(PDS)misdiagnosed as AFX were retrospectively analyzed by hematoxylin and eosin staining and immunohistochemical EnVision staining technology.Clinical information was collected and analyzed,and the relevant literatures were re-viewed.Results The age of the 15 patients with AFX ranged from 18 to 78 years,with an average age of 57 years.4 cases occurred in the head and neck,and 11 cases occurred in the trunk and limbs.3 patients with PDS misdiagnosed as AFX were aged from 56 to 60 years,with an average age of 58 years.The tumors were located in the trunk and limbs.Microscopically,15 cases of AFX and 3 cases of PDS misdiagnosed as AFX were composed of proliferative pleo-morphic and atypical spindle cells interspersed with a varying number of multinucleated cells.15 cases of AFX tumors were superficial and located in the dermis.In 3 cases of PDS misdiagnosed as AFX,1 case was located in subcutane-ous adipose tissue,1 case had superficial subcutaneous extension,and the third case had positive basal margin.Immu-nohistochemically,the immunophenotypes of the two groups were consistent.CD10 was expressed in all cases,CD68 was positive in most cases,SMA was expressed in a few cases,desmin was focal expressed in a very few cases,and S-100,SOX10,CD34,HMB-45,Melan A,STAT6 and CK(AE1/AE3)were not expressed in all cases.Ki67 prolifera-tion index ranged from 2％to 30％.15 patients with AFX were followed up from 12 to 108 months.One patient had tumor recurrence 1 year and 3 years after operation due to positive basal margin.Most of the other patients underwent extended resection after diagnosis and were in good condition without tumor recurrence and metastasis.3 cases of PDS misdiagnosed as AFX were followed up for 31 to 78 months.One patient had lung metastasis after 2 years,one patient recurred 4 times after operation,and the other patient died after 4 times of recurrence.Conclusion AFX is a rare dis-ease with similar pathological characteristics and immunophenotype to PDS.AFX can be diagnosed only when the tumor is small and completely confined to the dermis.When the maximum diameter of the tumor is more than 3 cm,or the presence of any form of subcutaneous extension requires a high level of vigilance for PDS.Careful differentiation and correct classification of AFX and PDS are very important for the treatment and prognosis of the disease.

Amid the wave of medical digitalalization,pathology departments urgently require digital and intelligent transformation to address challenges posed by surging clinical samples and resource shortages.Based on an interpreta-tion of the White Paper on the Development of Digital Intelligent Pathology Departments,this article proposes a"Four-Comprehensive"framework(encompassing all modules,full slide coverage,full workflows,and full ecosystem)as the core of intelligent pathology department development.It emphasizes a tiered implementation strategy,analyzes critical challenges and solutions,and provides tailored recommendations for hospitals at different levels.The paper further ad-vocates for industry-wide collaboration to establish unified data standards,accelerate the advancement of AI-driven pathological models and multimodal applications,and foster equitable resource distribution and precision medicine,thereby advancing China's digital-intelligent pathology ecosystem.