High-grade endometrial stromal sarcoma(HGESS)is a rare but highly aggressive malignant tumor that poses a significant threat to women's reproductive health.It is associated with a poor clinical prognosis due to its high malignancy.HGESS exhibits diverse pathological morphologies,lacks specific immunohistochemical markers,and demonstrates various genetic alterations.These factors contribute to the challenges in achieving a definitive diagnosis,making accurate identification and diagnosis of this lesion particularly difficult.This article reviews the clinicopathologi-cal features,molecular characteristics,and key points for differential diagnosis of HGESS,aiming to enhance under-standing and awareness of this disease among clinicians and pathologists.

Ovarian seromucinous tumors are a group of ovarian epithelial tumors that primarily affect young women of childbearing age.The nomenclature and classification of these tumors undergone a complex historical evolution.Due to their diverse and complex morphological features,pathologists often encountered difficulties in applying diagnostic criteria.As a result,underdiagnosis and misdiagnosis were common in current clinical practice,which may even affect the choice of treatment for patients.This article aims to provide a detailed account of the historical changes in the no-menclature of ovarian seromucinous tumors,the common diagnostic challenges encountered in current clinical practice and their corresponding strategies,as well as to explore potential future research directions.It is hoped that this will enhance the understanding of these diseases among pathologists and gynecologists,and provide guidance for the formu-lation of appropriate treatment strategies and further scientific research.

Purpose To investigate the clinicopathological characteristics,immunophenotype,high-risk human papillomavirus(hrHPV)infection status,treatment,and prognosis of cervical carcinoma exhibiting adenoid cystic car-cinoma(ACC)features.Methods Clinical data from 10 cases of cervical cancer with ACC features were collected.A retrospective analysis was proformed on the patients'clinicopathological data,histological features,and immunopheno-type(EnVision method),along with in situ hybridization detection of hrHPV E6/E7 mRNA covering 18 hrHPV types.Results The median age of the patients was 67.5 years,comprising 4 biopsy specimens and 6 surgical specimens.Except for 2 cases detected incidentally during physical examination,the remaining 8 cases presented with unexplained vaginal bleeding or contact bleeding.The mean tumor diameter was 4.5 cm(range:2.5 to 9.0 cm),and tumor stages were available for 8 patients(5 cases in stage Ⅰ and 1 case each in stages Ⅱ,Ⅲ,and Ⅳ).The follow-up period was 8 to 42 months,excluding 1 case lost to follow-up,2 cases(Ⅲ C1 and ⅣB)died within 1 year after surgery.Histologi-cally,4 cases exhibited pure ACC morphology,while 5 cases were mixed carcinomas(combined with squamous cell carcinoma,adenoid basal cell carcinoma,high-grade neuroendocrine carcinoma,or carcinosarcoma,respectively).The characteristic ACC morphology manifested as cribriform,pseudo-glandular,tubular,trabecular,and/or solid pat-terns with one case mixed carcinoma's lymph node metastasis showing only ACC morphology.Immunohistochemically,all 10 tumors exhibited diffuse strong positivity for p16 and p63,a high Ki67 proliferation index(40％to 90％),and wild-type p53 expression,and in 50％of cases,only a minority of cells were positive for c-MYB.Additionally,SOX10 was positive in 8 of 9 cases and CD117 was positive in 7 of 10 cases,respectively.In situ hybridization for hrHPV E6/E7 mRNA confirmed the presence of transcriptionally active HPV infection in all cases.Conclusion Cervical cancer with ACC features is rare,and predominantly occurs in postmenopausal elderly women.It represents an HPV-associat-ed high-grade carcinoma in which clinical stage is a critical prognostic factor.Immunohistochemical staining for CD117 and SOX10 aids in the pathological diagnosis of this tumor type.

Purpose To investigate the clinicopathological features and diagnosis of breast epithelial-myoepithelial tumors.Methods Collect 10 cases of breast epithelial-myoepithelial tumors.Clinical features,histopathologic fea-tures,immunophenotype,and molecular characteristics were analyzed.Results All patients were female,aged 27-49 years,and the maximum diameter of the mass was 1.5 to 6.0 cm.Among them,8 cases were diagnosed as adeno-myoepithelioma(AME)of the breast,1 case as atypical AME,and 1 case as malignant adenomyoepithelioma(AME-M).All ten patients were alive with no evidence of disease or metastasis,with follow-up periods ranging from 4 to 64 months.All epithelial-myoepithelial tumors consisted of proliferative epithelial and myoepithelial cells,with myoepithe-lial hyperplasia being the predominant component.In the atypical AME case,myoepithelial cells exhibited mild to moderate atypia,with mitotic figures observed occasionally(3/10 HPF).AME-M was composed of solid and cystic ar-eas.In the solid area,myoepithelial cells exhibited moderate to severe atypia with a high mitotic rate(6-8/10 HPF).Additionally,necrosis and areas of squamous cell carcinoma were present,leading to a diagnosis of epithelial-myoepithelial carcinoma.Papillary squamous cell carcinoma was found in cystic area and it involved the adjacent lob-ules.The peripheral breast tissue contained focal ductal carcinoma in situ.The luminal epithelial cells showed expres-sion of CK8/18 and CK7.The myoepithelial cells showed expression of p63,CD10,and SMA.The Ki67 index was less than 10％in AME,40％in atypical AME.In the AME-M,it was 80％in the epithelial-myoepithelial carcinoma component,and 70％in the papillary squamous cell carcinoma component.Sanger sequencing of 6 cases AME and 1 case atypical AME revealed no hotspot mutations in HRAS or PIK3CA.In one case of AME-M,pyrosequencing indica-ted no hotspot mutations of AKT1,KRAS,HRAS,and PIK3 CA in the components of epithelial-myoepithelial carcino-ma and papillary squamous cell carcinoma while one KRAS(c.183A＞C/T,p.Q61H)mutation was present in the peripheral ductal carcinoma in situ.Molecular genetic analysis on 22 short tandem repeat loci showed an identical pat-tern including LOH at D19S433 in both components of AME-M and squamous cell carcinoma.Conclusion AME is an rare tumor with a heterogeneous morphology.The biphasic proliferation of epithelial and myoepithelial components is the key to correct diagnosis.Molecular genetic analysis suggested AME-M and squamous cell carcinoma were clonally independent from the peripheral ductal carcinoma in situ.

Purpose To investigate the clinicopathological features,differential diagnosis,and prognosis of breast carcinoma within fibroadenoma(FA).Methods A retrospective analysis was performed on the clinical and imaging data of 21 cases of FA-associated carcinoma.HE staining,immunohistochemistry using the EnVision method,and next-generation sequencing were employed to assess the clinicopathological characteristics and genetic alterations,with a review of the relevant literature.Results All patients were female,aged 21-67 years,with a median age of 48 years.Clinically,all lesions presented with well-circumscribed mass lesions.On imaging,12 cases demonstrated punctate or coarse calcifications,while 3 cases exhibited locally indistinct margins.Pathological examination revealed that the tumors had an average maximum diameter of 2.25 cm,with a gray-white nodular cut surface resembling FA.Microscopically,there was proliferation of either epithelial or spindle cells.The pathological diagnosis was FA-associat-ed in situ carcinoma in 16 cases(15 cases of low-grade ductal carcinoma in situ and 1 case of lobular carcinoma in si-tu),and invasive carcinoma in 5 cases(comprising 2 cases of invasive carcinoma-no special type,1 case of invasive lobular carcinoma,1 case of low-grade adenosquamous carcinoma and 1 case of fibromatosis-like metaplastic carcino-ma).In 18 cases,the carcinoma was confined within the FA,whereas in 3 cases the tumor locally extended beyond the FA,and 1 case exhibited ipsilateral axillary lymph node metastasis.Immunophenotypically,tumor cells in in situ carcinomas were negative for CK5/6,while the myoepithelial cells were p63-positive,and both estrogen receptor(ER)and progesterone receptor(PR)were diffusely and consistently positive.In invasive carcinoma,both ductal and lobular subtypes were ER and PR positive and HER2 negative.Conversely,in the low-grade adenosquamous carcinoma and fi-bromatosis-like metaplastic carcinoma,ER,PR,and HER2 were all negative,with p63 and CK5/6 positivity.Two ca-ses were negative for mismatch repair protein PMS2.Six cases had a family or personal history of malignant tumors;a-mong the 5 cases that underwent next-generation sequencing,2 cases harbored germline BRCA2 mutations,2 cases had germline PMS2 mutations,and 1 case exhibited no definitive genetic alteration.Conclusion Carcinoma arising within FA exhibits atypical clinical and imaging features.In patients with high-risk factors for breast cancer or family history of malignancy,or when calcifications are observed on imaging,prompt excision and biopsy are recommended.Recogniz-ing the abnormal morphology within FA and the use of immunohistochemistry are essential for accurate diagnosis,with careful differentiation from spindle cell metaplastic carcinoma and low-grade adenosquamous carcinoma.Overall,the prognosis is relatively favorable,and treatment should be tailored according to tumor type,molecular subtype,and stage.

Purpose To investigate the clinicopathologic significance of VISTA and Foxp3 expression in triple-negative breast cancer(TNBC).Methods The expression of VISTA mRNA,Foxp3 mRNA in TNBC,along with their correlations with patient prognosis,were analyzed using GEPIA2 based on TCGA bioinformatics database.Sam-ples of 160 TNBC tissues and 160 normal breast tissues were collected.Immunohistochemical detection was proformed using the MaxVision 3HRP method to detect the expression of VISTA in both tumor cells and immune cells,and Foxp3 in tumor-infiltrating lymphocytes(TILs).Their differential expression,as well as the relationships with the clinico-pathological characteristics and prognosis in TNBC,were analyzed.Results Database analysis results showed that the expression level of VISTA mRNA in TNBC was lower than that in normal breast tissue(P＜0.05),while the expres-sion level of Foxp3 mRNA in TNBC was higher than that in normal breast tissue(P＜0.05).The expression of VISTA mRNA and Foxp3 mRNA in breast cancer tissues were positively correlated(rs=0.45,P＜0.001),and the expres-sion of VISTA mRNA was related to the overall survival.Immunohistochemical results showed that in TNBC,the posi-tive expression rate of VISTA in tumor cells was 15％(24/160),and 72.5％(116/160)in immune cells.The infil-tration density of Foxp3+TILs was higher than that in normal breast tissue(P＜0.001).The expression of VISTA in immune cells was positively correlated with Foxp3+TILs(rs=0.244,P=0.002).Moreover,the expression of VIS-TA in immune cells was related to the TNM stage of patients,and the infiltration density of Foxp3+TILs was related to the histological grade.Cox univariate and multivariate analyses indicated that TNM stage was an independent risk factor affecting the prognosis of TNBC patients.Conclusion In TNBC,VISTA is mainly expressed in immune cells and an increased infiltration density of Foxp3+TILs is observed.Both VISTA expression in immune cells and high infiltration density of Foxp3+TILs are correlated with clinicopathologic features indicative of poor prognosis,suggesting that they may act synergistically in the progression of TNBC.

Purpose To investigate the clinical,imaging,and pathological features of Kikuchi-Fujimoto disease(KFD).Methods A retrospective analysis was conducted on 123 pathologically confirmed KFD cases.Clinical and imaging data were collected,and histopathological features were evaluated using HE staining,immunohistochemistry,in situ hybridization for EBER,and molecular analyses(TCR/Ig gene rearrangements by PCR with capillary electro-phoresis).Results Among the 123 patients,the male-to-female ratio was 1∶2,with a median age of 30 years.All patients presented with lymphadenopathy.Among 30 hospitalized patients,63.3％(19/30)had fever,and 23.3％(7/30)had concurrent autoimmune diseases.Of the 12 patients who underwent PET-CT,91.7％(11/12)were sus-pected of malignancy,prompting biopsy recommendations.Among 47 consultation cases,27.7％(13/47)were ini-tially misdiagnosed as lymphoma.Histopathological examination revealed proliferative,necrotic,and xanthomatous phases,which coexisted or occurred independently.The proliferative phase was characterized by atypical lymphocytes and histiocytes,the necrotic phase by abundant eosinophilic fibrin deposits and nuclear debris,and the xanthomatous phase by clusters of foam-like histiocytes.Immunohistochemically analyses revealed that atypical lymphocytes were neg-ative for CD20,CD4,and CD56 but positive for CD3,CD8,TIA1,Granzyme B,and Perforin.Histiocytes expressed CD68,CD163,and MPO,while CD123-positive plasmacytoid dendritic cells were predominantly located around the le-sions and blood vessels.EBER was positive in individual cells in 4 cases.TCR gene rearrangement was positive in 2 cases and suspected positive in 3 cases,while Ig rearrangement was positive and suspected positive in 1 case each.Conclusion KFD exhibits clinical,imaging,and pathological features that can mimic lymphoma,highlighting the im-portance of accurate diagnosis to avoid misdiagnosis and inappropriate treatment.

Purpose To investigate the role of combined immunohistochemical expression of SATB2 and p16 and pathological histomorphological features in the diagnosis and differential diagnosis of atypical polypoid adenomyoma(APAM),myometrial infiltrating endometrioid carcinoma(MIEC)and interstitial fibrotic endometrial polyps(IFEP).Methods A total of 32 cases of APAM,20 cases of MIEC and 25 cases of IFEP were collected.The expression of SATB2 and p16 in the stromal cells of the three groups of cases was detected by immunohistochemical EnVision two-step method.Four morphological features were evaluated in the three groups:complex glandular structure,squamous and mulberry metaplasia,fibromuscular stroma and cellular atypia.Results The expression of SATB2 in the stroma of APAM(31/32)was significantly higher than that of MIEC(1/20)and IFEP(0/25),and the difference was statisti-cally significant.The expression of p16 in APAM(32/32)stroma was significantly higher than that in MIEC(3/20),and the difference was statistically significant,while compared with IFEP(21/25),the difference was not statistically significant.Histomorphological characteristics:compared with the MIEC group,APAM had obvious squamous and mul-berry metaplasia(APAM group 31/32,MIEC group 4/20),and the difference was statistically significant;However,there was no statistically significant difference between the two groups in terms of complex glandular structure(APAM group 22/32,MIEC group 20/20),fibromuscular stroma(APAM group 32/32,MIEC group 20/20),and cellular at-ypia(APAM group 32/32,MIEC group 20/20).Compared with the IFEP group,APAM had typical complex glandu-lar structure(APAM group 20/32,IFEP group 0/25),squamous and mulberry metaplasia(APAM group 32/32,IF-EP group 2/25),and cellular atypia(APAM group 32/32,IFEP group 0/25),and the difference was statistically sig-nificant.However,there was no statistically significant difference in fibromuscular stroma(APAM group 32/32,IFEP group 25/25)between the two groups.Conclusion The combined immunohistochemical analysis of SATB2 and p16 and histomorphological features is helpful for the diagnosis of APAM and the differential diagnosis of MIEC and IFEP.

Purpose To investigate the role of ultrasound-guided fine needle aspiration cytology(US-FNAC)in the diagnosis of breast cancer.Methods Fine needle aspiration cytology(FNAC)samples of 203 patients with breast cancer were selected and prepared by liquid-based cytology.The results of histopathology after neoadjuvant therapy were used as the gold standard to compare with the diagnostic results of FNAC samples,and then evaluated the diagnos-tic coincidence rate of FNAC samples.Results Of 203 axillary lymph node FNAC samples,111 cases were diagnosed as positive,38 cases were diagnosed as suspicious for positivity,and 54 cases were diagnosed as negative.The diag-nostic accuracy of FNAC was 85.2％,the sensitivity of FNAC was 98.0％,and the specificity of FNAC was 90.0％.Conclusion FNAC has high sensitivity and accuracy in the diagnosis of axillary lymph node metastasis.Sentinel lymph node biopsy is recommended for patients with negative FNAC but clinically and radiographically suspected lymph node metastasis.

Purpose To investigate the predictive value of the methylation regulator heterogeneous nuclear ribonu-cleoprotein C(HNRNPC)in the extracellular vesicles(EVs)derived from cervical cancer cells for tumor invasion and metastasis.Methods In vitro experiments were conducted using a human normal cervical epithelial cell line(Hcer-Epic),three cervical cancer cell lines(HeLa,SiHa and CaSki)and human umbilical vein endothelial cells(HU-VECs).HNRNPC protein expression was assessed by Western blot.CaSki cells were transfected with either sh-NC or sh-HNRNPC,and EVs were subsequently isolated from culture supernatant.The effects of EVs on the proliferation,migration and invasion of SiHa cells,as well as on angiogenesis in HUVECs,were investigated respectively.For tissue microarray analysis,normal cervical tissues(n=8),low-grade squamous intraepithelial lesions(LSIL,n=32)and high-grade squamous intraepithelial lesions(HSIL,n=37),and cervical carcinoma specimens(n=153)were ob-tained from our institution.Based on HNRNPC immunoscores,cervical cancer patients were divided into two groups:high(n=99)and low(n=54)HNRNPC expression group,and their clinicopathological features and prognosis were compared.Results Compared with HcerEpic cells,the expression of HNRNPC increased in SiHa,HeLa and CaSki cells.In SiHa cells treated with EVs from CaSki cell,the group receiving EVs from sh-HNRNPC-transfected CaSki cells showed significantly reduced proliferation,colony formation,migration,and invasion compared with the sh-NC-EVs group(P＜0.05).Similarly,in HUVECs treated with CaSki-EVs,compared with sh-NC-EVs group,the sh-HNRNPC-EVs group demonsteated significantly lower protein expression of PCNA and VEGFA and reduced angiogene-sis length(P＜0.05).HNRNPC expression gradually increased during the transformation of cervical epithelial cells(F=106.9,P＜0.001),and was significantlyelevated in HSIL and cervical cancer tissues compared with normal tis-sues(P＜0.001).Moreover,in cervical cancer,high HNRNPC expression was significantly related to poorer cellular differentiation,larger tumor size,parametrial and vaginal infiltration,advanced FIGO stage,and pelvic lymph node metastasis(P＜0.05).Kaplan-Meier analysis showed that that patients with high HNRNPC expression had significant-ly shorter overall survival post-surgery compared with those with low expression(P＜0.05).Conclusion EVs contai-ning HNRNPC contribute to cervical cancer progression by promoting tumor growth,invasion,and angiogenesis,there-by accelerating metastasis.In addition,high HNRNPC expression in cervical cancer tissue is related to poor prognosis of patients,indicating that EV-associated HNRNPC may serve as a potential therapeutic target.