Objective:To investigate the clinical, imaging and neuropathological characteristics of neuronal intranuclear inclusion disease (NIID) with symptoms of the central nervous system, and to improve the diagnosis and treatments of NIID.Methods:The clinical data of 7 patients with NIID diagnosed by brain biopsy in Xuanwu Hospital, Capital Medical University, Beijing, China from February 2009 to December 2024 were collected. The characteristics of clinical manifestations, imaging, and histology on brain biopsy were retrospectively analyzed.Results:Among the 7 patients, 5 were male and 2 were female. Their ages ranged from 44 to 70 years, median 56 (52, 65) years. Patients were classified into three types of tumor, stroke and encephalitis according to the onset symptoms, imaging manifestations and pathological changes. The chief complaint of the 5 patients was headache, while 4 patients had paroxysmal convulsions, 3 had speech disorders, 2 had abnormal mental behaviors, 2 had memory decline, and 1 had fever accompanied by consciousness disorders. Diffusion-weighted magnetic resonance imaging of the head showed the "ribbon sign" at the junction of the cortex and medulla in 2 cases. Most of the patients had white matter lesions, gyrus swelling and cerebral atrophy. Occasionally gyrus-like enhancement was observed. Brain biopsy reveals the histological changes that matched those on images and initial symptoms. There were proliferation of oligodendrocytes and astrocytes in the white matter, leukoaraiosis and edema, cortical disintegration and lamellar necrosis, as well as infiltration of lymphocytes and microglia, etc. However, the characteristic changes were eosinophilic hyaline inclusions in the nuclei of neurons and astrocytes. Immunohistochemical staining of p62 and ubiquitin showed homogeneous staining in round or ring-shaped nuclei.Conclusions:The clinical manifestations of NIID are highly variable, and a correct diagnosis of NIID requires careful integration of clinical, imaging and histopathologic data. For patients with a high suspicion of NIID, immunohistochemical staining of p62 and ubiquitin is diagnostically valuable.

Objective:To investigate the clinicopathological characteristics of lung transplantation and post-transplantation changes in patients with pneumoconiosis.Methods:A retrospective study was conducted to analyze the clinical and pathological data of 28 patients with pulmonary silicosis who underwent lung transplantation and were managed at the Department of Internal Medicine, Henan Provincial People′s Hospital, Zhengzhou, China from January 2015 to December 2024. Among them, 8 patients underwent lung biopsy 6-20 months after transplantation to evaluate the histopathological changes of the recipient and the donor lungs post-transplantation. The expression of relevant indicators was examined using immunohistochemical EnVision staining, while presence of microorganisms was assessed using histochemical special staining. The patients were all followed up.Results:Among the 28 patients with pneumoconiosis who underwent lung transplantation, 26 were male and 2 were female, with a male-to-female ratio of 13∶1. Their ages ranged from 23 to 68 years, median 50.0 (46.0, 53.5) years. They were diagnosed with pneumoconiosis at local occupational disease prevention and control centers for 3 to 15 years (mean, 9.65 years), including 13 left single lung transplants and 15 right single lung transplants. Gross examination showed fleshy nodules with irregular cystic cavities at the periphery. The cut surfaces exhibited gray-brown color and firm texture. Microscopically, most alveolar structures of the lung were obliterated, with nodular or diffuse proliferation of collagen fibers accompanied by hyaline degeneration. Focal massive carbon dust deposition and massive silicotic fibrosis were observed, surrounded by lung parenchyma with emphysematous changes and localized bullae formation. Seven patients underwent re-biopsy after transplantation that showed extensive infiltration of inflammatory cells. In 4 cases, microscopy revealed complete coagulative necrosis, with negative acid-fast staining and TB-DNA results. Of the 4 cases, 3 cases exhibited Aspergillus infection confirmed by Grocott′s methenamine silver and PAS stains, while 2 cases showed chronic bronchitis with squamous metaplasia. Follow-up revealed that 8 patients died of acute respiratory failure due to severe infection, while the remaining 20 demonstrated significant postoperative improvement in lung function.Conclusions:For patients with advanced pulmonary dust deposition disease who undergo lung transplantation, it is necessary to conduct standardized sampling and pathological assessment of the recipient lungs. In the early post-transplant period, the complications of re-biopsy tissues are mainly fungal infections. The combination of morphological manifestations and immunohistochemical detection is helpful to distinguish infection from rejection reactions. At the same time, it is essential to integrate clinical information and laboratory results to provide post-transplantation pathological assessment for individualized treatment.

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.

The 2022 5th edition WHO Classification of Haematolymphoid Tumours introduces significant revisions to histiocytic and dendritic cell neoplasms,involving the reclassification and renaming of certain diseases alongside the addition of new distinct entities.This article systematically interprets these updates and summarizes the key points for the diagnosis and differential diagnosis of histiocytic neoplasms,aiming to enhance diagnostic accuracy and treatment outcomes for this disease group.

Purpose To investigate the clinicopathological features and molecular genetic alteration of Epstein-Barr virus-positive diffuse large B-cell lymphoma(EBV+DLBCL)in pediatric patients.Methods Clinical data were collected for 3 pediatric patients diagnosed with EBV+DLBCL.Immunohistochemistry(EnVision two-step method)was used to evaluate expression of CD20,CD79α,CD3,CD5,CD30,EBNA2,Fascin,and GATA3.In situ hybridization detected EBER1/2 expression.B-cell receptor(BCR)and T-cell receptor(TCR)gene rearrangements were performed to evaluate the clonal rearrangement of tumor lymphocytes.Results Among the 3 pediatric patients(ages 13-18),there were 2 males and 1 female.All patients presented with painless lymphadenopathy without bone marrow involve-ment.One female patient exhibited B symptoms(fever,night sweats,and weight loss),whereas both male patients were asymptomatic.According to the Lugano classification,2 cases were stage Ⅲand one was stage Ⅳ.Histopathologi-cally,2 cases exhibited a polymorphic morphology resembling T-cell/histiocyte-rich large B-cell lymphoma,and one case demonstrated monomorphic morphology typical of conventional DLBCL.Immunophenotypically,all cases strongly expressed various B-cell transcription factors;CD30 expression varied in intensity;EBNA2,Fascin and GATA3 were uniformly negative.In situ hybridization indicated EBER1/2 positive expression in large tumor cells and scattered back-ground small lymphocytes.Clonal Ig gene rearrangement peaks were detected in all 3 cases.Each patient received standard DLBCL chemotherapy,and follow-up PET-CT scans indicated complete remission in all.Conclusion Pediat-ric EBV+DLBCL is rare,and diagnosing the polymorphic subtype poses particular challenges.In China,many patholo-gists consider detection of clonal Ig gene rearrangement as the diagnostic"gold standard".Even when clinical course and imaging data strongly support EBV+DLBCL,final diagnosis can remain controversial.Further accumulation of ca-ses and long-term follow-up are needed to elucidate optimal diagnostic criteria,treatment responses,and prognostic fac-tors.