Expression and Prognostic Significance of LAG-3, TIGIT, VISTA, and IDO1 in Endometrial Serous Carcinoma.

Endometrial serous carcinoma (ESC) is an uncommon, aggressive type of endometrial cancer. While immune checkpoint blockade has emerged as a promising treatment option for endometrial carcinomas, research on the expression of immune checkpoints that could serve as prospective immunotherapy targets in ESC is limited. We examined the prevalence and prognostic value of LAG-3, TIGIT, VISTA, and IDO1 in 94 cases of ESC and correlated their expression with CD8+ and FOXP3+ tumor infiltrating lymphocytes (TIL). We observed a positive correlation between LAG-3, TIGIT and VISTA expressed on immune cells, and between these markers and CD8+ and FOXP3+ TIL density. In Kaplan-Meier survival analysis, tumors with high levels of LAG-3 and TIGIT expression had better progression free survival (PFS) and overall survival (OS) than those with lower levels of expression (LAG-3: PFS, p=0.03, OS, p=0.04; TIGIT: PFS, p=0.01, OS, p=0.009). In multivariate analysis, only high TIGIT expression was of independent prognostic value for better overall survival. VISTA expression in immune or tumor cells, and IDO1 expression in tumor cells, did not show a significant association with survival. Our data indicate that LAG-3, TIGIT, and VISTA immune checkpoints have roles in the microenvironment of ESC, and their expression patterns highlight the complex interactions among the different components of this system. High levels of these markers, together with high CD8+ TIL, suggests the potential immunogenicity of a subset of these tumors. Further studies are needed to elucidate the roles of various immune components in the ESC microenvironment and their association with intrinsic tumor properties.

Biomarkers in the Diagnosis of Endometrial Precancers. Molecular Characteristics, Candidate Immunohistochemical Markers, and Promising Results of Three-Marker Panel: Current Status and Future Directions.

Endometrial carcinoma stands as the most prevalent gynecological cancer and the fourth most common cancer affecting women. The incidence of endometrial cancer has been steadily increasing over the past decade, posing a significant threat to public health. The early detection of its precancers remains a critical and evolving concern to reduce mortality associated with endometrial carcinoma. In the last decade, our understanding of endometrial carcinoma and its precancers has advanced through systematic investigations into the molecular genetics of endometrial carcinoma and its precancers. In this review, we focus on advances in precancers associated with the endometrioid subtype, by far the most common histologic variant of endometrial adenocarcinoma. Recent investigations have led to the identification of new biomarkers, and the proposed incorporation of these biomarkers or biomarker panels into the diagnostic framework of endometrial carcinoma precancers. Here, we review these recent advances and their relevance to the histopathologic diagnosis of endometrial carcinoma precancers.

Prevalence of cervical precancers or cancers in women with ASC-H/HSIL cytology according to Aptima HPV (AHPV) assay-detected HPV genotypes and age.

Objective: Aimed to potentially risk-stratify patients with different cervical cytology diagnoses, by HPV genotypes and/or age, we have conducted a series of studies to examine the prevalence of cervical precancers and cancers for women with different cytology diagnoses. This paper will be focusing on patients with ASC-H/HSIL cytology. Methods: In total, 1183 patients aged 20-78 years with atypical squamous cells, cannot rule out HSIL (ASC-H)/HSIL by cytology underwent AHPV assay and cervical biopsy in a developed region in southern China were included in this study. Results: Overall, 59.2% women with ASC-H/HSIL cytology had cervical intraepithelial neoplasia (CIN)2/3 lesions while 1.6% had adenocarcinoma in situ (AIS) lesions. Compared to other groups, HPV-16+ group (80.8%) showed a significantly higher prevalence of CIN2/3 than other genotype+ groups (p<0.0001). Further, HPV-16+ (9.3%) or HPV-18/45+ (6.3%) group showed a significantly higher prevalence of squamous cell carcinoma (SCC) than other genotype+ groups (p<0.0001). The prevalence of AIS glandular lesions in HPV-18/45+ group (13.8%) is significantly higher than other genotype groups (p<0.0001). When stratified by age, younger group showed a significantly higher prevalence of CIN2/3 (p=0.009) while older group presented an obvious higher prevalence of SCC (p<0.0001). Conclusions: In this patient population, among women with ASC-H/HSIL cytology, HPV positive groups are at significantly higher risk of CIN2/3 compared to HPV negative group. Specifically, prevalence of CIN2/3 and SCC is significantly higher in HPV-16+ group while AIS lesions are more prevalent among HPV-18/45+ patients. In addition, younger group showed a significantly higher prevalence of CIN2/3 while older group presented an obvious higher prevalence of SCC.

Correlation of immediate prevalence of cervical precancers and cancers with HPV genotype and age in women with ASC-US/hrHPV+: a retrospective analysis of 2292 cases.

AIMS: To stratify the risk of cervical precancers (high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS)) and cancers (squamous cell carcinoma (SCC) and adenocarcinoma) based on distinct high-risk human papillomavirus (hrHPV) genotypes as well as age groups among women with atypical squamous cells of undetermined significance (ASC-US) and hrHPV+results. METHODS: In total, 2292 cases of ASC-US/hrHPV+ with immediate follow-up biopsy results were included in the study for prevalence analysis. RESULTS: Overall, 12.2% women with ASC-US /hrHPV+ had HSIL+ while 0.22% had AIS+ lesions. The HPV-16+ group (31.6%) showed significantly higher prevalence of HSIL+ squamous lesions than other genotype groups (p<0.0001). The prevalence of SCC is significantly higher in HPV-16+ (1.8%) or HPV-18/45+ (1.1%) group than women in other genotype groups (0.1%) (p<0.0001). The HPV-18/45+ group (1.7%) showed significantly higher prevalence of AIS+ glandular lesions than other genotype groups (p=0.003). In addition, SCC prevalence was significantly higher in age over 50 group than that in age under 50 group (1.2% vs 0.2%, p=0.012). CONCLUSION: Women with ASC-US/hrHPV+ are at significant risk of cervical precancers and cancers; notably, HPV-16+ group has a higher risk of HSIL squamous lesions and SCC while HPV-18/45+ group has a higher risk of AIS+ glandular lesions. In addition, the older patient group (>50 years) has a significantly higher risk of SCC. Therefore, HPV genotyping as well as patient age need to be considered in the clinical management of patient.

Endometrioid Adenocarcinoma With "Burrowing" Invasion of the Cervix Represents a Separate Primary From the Concurrent Uterine Corpus Endometrial Endometrioid Adenocarcinoma: Histology, Immunohistochemistry, and Next-generation Sequencing Study of a Single Case.

A small subset of endometrial endometrioid adenocarcinoma cases first reported in 2003, showed a distinct cervical component with a so-called "burrowing" invasion pattern. Initially, the cervical component was regarded as cervical involvement by the endometrial adenocarcinoma. However, a 2010 study argued that these cases actually might represent separate primary endometrial and cervical endometrioid adenocarcinomas. However, additional data on this topic are scarce. Here, we report a case of endometrioid adenocarcinoma with a "burrowing" cervical invasion that is morphologically distinct from the patient's endometrial endometrioid adenocarcinoma. By comparing the morphology, immunophenotype, and genetic profile obtained by next-generation sequencing, we demonstrated that the cervical and endometrial tumors were of 2 separate primaries. Our report adds additional data to this unique phenomenon, and will hopefully help to reignite interest in investigating this controversial topic.

An integrated model for prognosis in vulvar squamous cell carcinoma.

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) is a relatively rare gynecologic cancer. Unlike cervical squamous cell carcinoma (CSCC), in which nearly all cases are caused by HPV infection, most VSCCs are HPV-independent. Patients with VSCC also have worse overall survival (OS) than those with CSCC. Unlike CSCC, the risk factors of VSCC have not been extensively studied. Here, we investigated the prognostic values of clinicopathological parameters as well as biomarkers in patients with VSCC. METHODS: In total, 69 cases of VSCC accessions were selected for analysis between April 2010 and October 2020. The risk factors of VSCC were screened using Cox models to establish nomograms for predicting survival outcomes. RESULTS: Following the multivariate COX model for OS, independent predictors including advanced age (hazard ratio [HR] 5.899, p = 0.009), HPV positivity (HR 0.092, p = 0.016), high Ki-67 index (HR 7.899, p = 0.006), PD-L1-positivity (HR 4.736, p = 0.077), and CD8 + tumor-infiltrating lymphocytes (TILs) (HR 0.214, p = 0.024) were included in the nomogram for OS; multivariate COX model for progression-free survival (PFS) was used to screen prognostic factors including advanced age (HR 2.902, p = 0.058), lymph node metastasis (HR 5.038, p = 0.056), HPV positivity (HR 0.116, p = 0.011), high Ki-67 index (HR 3.680, p = 0.042), PD-L1-positivity (HR 5.311, p = 0.045), and CD8 + TILs (HR 0.236, p = 0.014) to establish the PFS nomogram model. Based on the C-index (0.754 for OS and 0.754 for PFS) from our VSCC cohort and the corrected C-index (0.699 for OS and 0.683 for PFS) from an internal validation cohort, the nomograms demonstrated good predictive and discriminative ability. Kaplan-Meier curves also supported the excellent performance of the nomograms. CONCLUSION: Our prognostic nomograms suggested that (1) shorter OS and PFS were associated with PD-L1-positivity, high Ki-67 index, and low CD8 + TILs; (2) HPV-independent tumors were associated with poorer survival outcome, and mutant p53 status showed no prognostic significance.

Utility of a PAX2, PTEN, and ß-catenin Panel in the Diagnosis of Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia in Endometrial Polyps.

The diagnosis of atypical hyperplasia/endometrioid intraepithelial neoplasm (AH/EIN) within endometrial polyps (EMPs) often poses a diagnostic conundrum. Our previous studies demonstrated that a panel of immunohistochemical (IHC) markers consisting of PAX2, PTEN, and ß-catenin can be effectively utilized for the identification of AH/EIN. A total of 105 AH/EIN within EMP were analyzed using the 3-marker panel. We also evaluated these cases for the presence of morules. Benign EMP (n=90) and AH/EIN unassociated with polyp (n=111) served as controls. Aberrant expression of PAX2, PTEN, or ß-catenin was observed in AH/EIN in EMP in 64.8%, 39.0%, and 61.9% of cases, respectively. At least 1 IHC marker was abnormal in 92.4% of cases. Overall, 60% of AH/EIN in EMP demonstrated abnormal results for≥2 IHC markers. The prevalence of PAX2 aberrancy was significantly lower in AH/EIN in EMP than in nonpolyp AH/EIN (64.8% vs. 81.1%, P =0.007), but higher than in benign EMP (64.8% vs. 14.4%, P <0.00001). The prevalence of ß-catenin aberrancy was significantly higher in AH/EIN in EMP than in nonpolyp AH/EIN (61.9% vs. 47.7%, P =0.037). All control benign EMP demonstrated normal expression of PTEN and ß-catenin. Morules were present in 38.1% of AH/EIN in EMP versus 24.3% in nonpolyp AH/EIN, and absent in benign EMP. A strong positive association was found between ß-catenin and morules (Φ=0.64). Overall, 90% cases of atypical polypoid adenomyoma (n=6) and mucinous papillary proliferation (n=4) showed IHC marker aberrancy. In conclusion, the 3-marker IHC panel (PAX2, PTEN, and ß-catenin) is (1) a useful tool in the diagnosis of AH/EIN in EMP; (2) PAX2 loss should be interpreted with caution and in combination with morphology and other markers.

Primary cardiac angiosarcoma initially diagnosed on pericardial fluid cytology with histology and autopsy correlation.

Primary cardiac angiosarcoma is an exceedingly rare high-grade malignancy of the heart originating from endothelial cells, with a predilection for the right atrium in male. Clinical diagnosis is extremely challenging because of the nonspecific symptoms and radiological findings. Although almost always presenting with massive recurrent pericardial effusions, cardiac angiosarcoma diagnosed based on pericardial fluid has rarely been reported, either due to the paucity of malignant cells or misdiagnosis due to low familiarity/suspicion and lack of proper workup. Unfortunately, patients with this disease often receive definitive diagnosis post-mortem. We report a case of primary cardiac angiosarcoma initially diagnosed on pericardial fluid. The cytomorphology and immunophenotype of angiosarcoma in fluid, as well as the challenges and practical recommendations in using pericardial fluid cytology for early diagnosis of this deadly disease are discussed.

Aggressive High-grade Uterine Sarcoma Harboring MEIS1-NCOA2 Fusion and Amplification of Multiple 12q13-15 Genes: A Case Report With Morphologic, Immunohistochemical, and Molecular Analysis.

MEIS1-NCOA1/2 fusions are recently described gene rearrangements found in rare sarcomas, mainly involving the genitourinary and gynecologic tracts, with 3 cases reported in the uterine corpus. Although local recurrence was very common, no death has been reported, and some investigators consider these sarcomas low grade. Amplification of genes located at the 12q13-15 locus, especially MDM2 , is the hallmark genetic abnormality in well-differentiated and dedifferentiated liposarcoma of the soft tissue. Some uterine tumors have also been reported to harbor MDM2 amplification, including a proportion of Müllerian adenosarcomas, BCOR fusion-positive high-grade endometrial stromal sarcoma, BCORL1 -altered high-grade endometrial stromal sarcoma, rare JAZF1 fusion-positive low-grade endometrial stromal sarcoma, rare undifferentiated uterine sarcoma, and a single case of MEIS1-NCOA2 fusion sarcoma. Here, we report a case of high-grade MEIS1-NCOA2 fusion uterine sarcoma which also harbored amplification of multiple 12q13-15 genes, including MDM2 , CDK4 , MDM4 , and FRS2 , that exhibited aggressive clinical course leading to patient's death within 2 yr of the initial diagnosis. To the best of our knowledge, this is the first documented case of fatal MEIS1-NCOA2 fusion uterine sarcoma, and the second case of MEIS1-NCOA2 fusion uterine sarcoma that also harbors MDM2 amplification.

Discordance of PD-L1 expression in primary and metastatic ovarian high-grade serous carcinoma and its correlation with CD8 + tumor-infiltrating lymphocytes and patient prognosis.

Differential expression of programmed death-1 ligand (PD-L1) and its clinical significance in primary and metastatic ovarian high-grade serous carcinoma (HGSC) have not been defined. Thus, we investigated the PD-L1 expression of paired ovarian primary and omental metastatic HGSC and its correlation with CD8 + tumor-infiltrating lymphocyte (TILs) and patient survival. A total of 212 cases of ovarian HGSCs with matched primary ovarian and metastatic omental tumors accessioned between 2003 and 2018 were selected for further analysis. Using immunohistochemistry, we evaluated the density of CD8 + TILs and expression of PD-L1 on whole tissue sections. Applying tumor proportion score (TPS, cutoff 1%) and combined positive score (CPS, cutoff 1), the prevalence of PD-L1 expression was similar but with significant discordance in ovarian and omental tumor. Using TPS, patients with PD-L1-positive tumors demonstrated significantly worse recurrence free survival (RFS) and overall survival (OS) than patients with PD-L1-negative tumors. Using CPS, patients with PD-L1-positive ovarian tumors demonstrated significantly worse OS while no significant difference in RFS was found. Patients with PD-L1-positive omental tumors demonstrated significantly worse RFS and OS. Patients with omental PD-L1-positive tumors (TPS) were associated with poorer RFS and OS, while patients with ovarian PD-L1-positive tumors (TPS) were associated with OS not RFS, in COX multivariant analysis. Nonetheless, ovarian and omental high CD8 TILs density was not associated with worse OS in univariant and COX multivariant analysis. PD-L1 expression in ovarian and omental tumor associated with an increased CD8 + TILs density. PD-L1 expression by TPS was better correlated with survival than by CPS, and PD-L1 expression in omental tumors was a stronger prognostic indicator than that in ovarian tumors.

Assessment of HER2 in Gastric-Type Endocervical Adenocarcinoma and its Prognostic Significance.

As the most common type of human papillomavirus-independent endocervical adenocarcinomas (ECAs), gastric-type endocervical adenocarcinomas (GEAs) account for approximately 10% of all ECAs. Although anti-HER2 therapy has been proven effective in many cancers, it has not been used in ECAs, including GEAs, which is at least partly due to the lack of a well-defined guideline. Limited available data regarding HER2 in GEAs and ECAs have considerable variations likely caused by variations in the tumor type selection, testing methods, and scoring criteria. Here, we selected 58 GEA cases to examine the HER2 status using immunohistochemistry and fluorescent in situ hybridization and investigate the prognostic value and their association with other known or potential prognostic factors. When strong complete or lateral/basolateral membranous reactivity in ≥10% tumor cells was used to define HER2 positivity, relatively high prevalence of HER2 overexpression (10/58[17.2%]) and amplification (9/58 [15.5%]), as well as high immunohistochemistry-fluorescent in situ hybridization concordance rate (9/10 [90%]) was found in GEAs. A lateral/basolateral staining pattern ("U-shaped") was observed, at least focally, in most of HER2-positive (3+) and equivocal (2+) tumors. Notably, considerable heterogeneity of HER2 expression was observed in HER2 positive and equivocal cases (80.0% and 83.3%, respectively). HER2 overexpression and amplification were associated with worse progression-free survival (P = .047 and P = .032, respectively). Programmed death-ligand 1 expression was associated with worse progression-free survival (P = .032), whereas mutant-type p53 demonstrated no prognostic significance. Our work laid a solid foundation for the eventual development of a future standard HER2 testing guideline for GEAs.

Ovarian Microcystic Stromal Tumor With Intraovarian Recurrence and Peritoneal and Omental Spread: A Case Report With Morphological, Immunohistochemical, and Molecular Analysis.

Microcystic stromal tumors (MCSTs) are rare ovarian stromal tumors. They harbor CTNNB1 or APC mutations, resulting in ß-catenin nuclear expression. To date, all MCST cases treated with oophorectomy or more extensive surgery have followed benign clinical courses. However, 1 of the 3 cases treated with ovarian cystectomy/tumor resection recurred in the residual ovary and iliac fossa 9 years after ovarian cystectomy. Here, we report a case of recurrent MCST in a 38-year-old woman. The patient underwent ovarian cystectomy for a 7.5 cm solid-cystic right ovarian mass, which showed classic morphological and immunophenotypical features of MCST. Four years later, the tumor recurred in the residual right ovary as a 21 cm mass, involving the pelvic peritoneum and omentum. Molecular analysis using next-generation sequencing revealed a single C TNNB1 exon 3 S37A mutation in the recurrent tumor. To the best of our knowledge, this is the second case of recurrent MCST, which presents more evidence that MCST has the potential to recur and spread locally. Rather than ovarian cystectomy/tumor resection, more aggressive surgery, such as unilateral oophorectomy, may be necessary to decrease the risk of recurrence. Long-term postsurgery follow up is needed, especially after simple ovarian cystectomy/tumor resection.

Prevalence and prognostic significance of PD-L1, TIM-3 and B7-H3 expression in endometrial serous carcinoma.

Endometrial serous carcinoma (ESC) is an aggressive type of endometrial carcinoma with a poor prognosis. Immune checkpoint blockade has evolved as a novel treatment option for endometrial cancers; however, data on expression of immune checkpoints that may be potential targets for immunotherapy in ESC are limited. We analyzed the prevalence and prognostic significance of PD-L1, TIM-3 and B7-H3 immune checkpoints in 99 ESC and evaluated their correlation with CD8 + tumor infiltrating lymphocytes. Applying the tumor proportion score (TPS) with a cutoff of 1%, PD-L1, TIM-3 and B7-H3 expression was present in 17%, 10% and 93% of cases, respectively. Applying the combined positive score (CPS) with a cutoff of 1, PD-L1, TIM-3 and B7-H3 expression was present in 63%, 67% and 94% of cases, respectively. Expression of these markers was largely independent of one another. PD-L1 correlated with higher CD8 + T-cell density when evaluated by either TPS (p = 0.02) or CPS (p < 0.0001). TIM-3 correlated with CD8 + T-cell density when evaluated by CPS (p < 0.0001). PD-L1 positivity was associated with improved overall survival (p = 0.038) when applying CPS. No association between PD-L1 expression and survival was found using TPS, and there was no association between TIM-3 or B7-H3 positivity and survival by either TPS or CPS. Using TPS, PD-L1 correlated with a higher tumor stage but not with survival, whereas the converse was true when PD-L1 was evaluated by CPS, suggesting that PD-L1 expression in immune cells correlates with prognosis and is independent of tumor stage. In conclusion, PD-L1, TIM-3 and B7-H3 may be potential therapeutic targets in selected patients with ESC. Further investigation of their roles as predictive biomarkers is needed.

Morules But Not Squamous Differentiation are a Reliable Indicator of CTNNB1 (ß-catenin) Mutations in Endometrial Carcinoma and Precancers.

Although collectively regarded as "squamous differentiation (SD)" in endometrial endometrioid carcinoma (EEC) and atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), morules (often referred to as "squamous morules") and true SD may represent two distinct phenomena. Here, we explored the distinction between morules versus SD and investigated the association of morules and SD with CTNNB1 mutations. A total of 270 cases of EEC and AH/EIN were studied, including EEC with (n=36) or without (n=36) morules and AH/EIN with (n=80) or without (n=118) morules. Cases were analyzed by immunohistochemistry and selected cases (n=20) by targeted next-generation sequencing panel. Near-perfect agreement was found between morules and glandular ß-catenin nuclear staining in AH/EIN and EEC. A strong positive association was found between morules and glandular ß-catenin nuclear staining ( P <0.0001, Φ=0.59 in AH/EIN; P <0.0001, Φ=0.85 in EEC). There was no association between (1) morules and glandular PAX2 or PTEN aberrant expression or (2) SD and aberrant expression of ß-catenin, PAX2 or PTEN (Φ=0.09, ß-catenin; Φ=0.16, PAX2; Φ=0.13, PTEN). CTNNB1 mutations were identified in all 20 selected morule-containing cases (100%). Next-generation sequencing was performed on 2 (preprogestin and postprogestin treatment) biopsies from 1 patient, revealing identical mutational profile in morules and glands. In conclusion, (1) SD and morules are distinct biological phenomena; (2) the presence of morules, but not SD, is a reliable indicator of CTNNB1 mutations in EEC and AH/EIN. Our findings demonstrate that SD and morules are distinct biological phenomena. Since morules but not SD are associated with ß-catenin mutations, the distinction is clinically relevant and should be included in diagnostic reports.

[Effectiveness analysis of lateral condyle sliding osteotomy in total knee arthroplasty for the treatment of lateral femoral bowing deformity].

OBJECTIVE: To investigate the effectiveness of lateral condyle sliding osteotomy (LCSO) in total knee arthroplasty (TKA) for the treatment of lateral femoral bowing deformity. METHODS: The clinical data of 17 patients with lateral femoral bowing deformity treated by LCSO during TKA between July 2018 and July 2020 was retrospectively analysed. There were 3 males and 14 females, with an average of 63.2 years (range, 58-68 years). The etiology of lateral femoral bowing deformity included 12 cases of femoral developmental deformity and 5 cases of femoral fracture malunion. Kellgren-Lawrence classification of knee osteoarthritis was 4 cases of grade Ⅲ and 13 cases of grade Ⅳ. The preoperative hip-knee shaft was 9.5°-12.5° (mean, 10.94°). The disease duration was 3-25 years (mean, 15.1 years). The mechanical lateral distal femur angle (mLDFA), hip-knee-ankle angle (HKA), and mechanical axis deviation (MAD) of the distal femur were measured before operation and at last follow-up to evaluate the correction of extra-articular deformities in the joints and the recovery of mechanical force lines of the lower extremities. The knee society score (KSS) knee score and function score, visual analogue scale (VAS) score, knee joint range of motion (ROM) were used to evaluate effectiveness. The knee varus/valgus stress test and osteotomy healing by X-ray films were performed to evaluate the joint stability and the safety of LCSO. RESULTS: All incisions of the patients healed by first intention after operation, and there was no early postoperative complication such as infection of the incision and deep vein thrombosis of the lower extremities. All 17 patients were followed up 12-36 months, with an average of 23.9 months. The osteotomy slices all achieved bony healing, and the healing time was 2-5 months, with an average of 3.1 months. After operation, the knee varus/valgus stress tests were negative, and there was no relaxation and rupture of the lateral collateral ligament, instability of the knee joint, loosening, revision and infection of the prosthesis occurred. At last follow-up, mLDFA, HKA, MAD, knee ROM, VAS score, KSS knee score and function score significantly improved when compared with preoperative ones ( P<0.05). CONCLUSION: LCSO is effective and safe in TKA with lateral femoral bowing deformity. Extra-articular deformities are corrected intra-articularly. The mechanical force line and joint balance of the lower extremities can be restored simultaneously in an operation.

Endometrial stromal tumors: Diagnostic updates and challenges.

Endometrial stromal tumors are rare uterine mesenchymal tumors of endometrial stromal origin. They are classified into endometrial stromal nodule, low-grade endometrial stromal sarcoma, high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma by the current (2020) WHO classification. Correct diagnosis of endometrial stromal tumors is critical for proper patient management. However, due to infrequent encounters, overlapping morphological features and immunohistochemical profiles, the differential diagnoses among endometrial stromal lesions and their morphologic mimics are often challenging. Partially with our own experience, here we review and summarize the tumor morphology, immunohistochemical phenotype, as well as molecular feature of endometrial stromal tumors and key differential diagnoses, emphasizing the newest developments and their utilization in daily practice.

A prospective observational study of persistent opioid use after complex foot and ankle surgery.

PURPOSE: The incidence of persistent postsurgical opioid use (PPOU) after complex foot and ankle surgery is unknown. We aimed to determine the incidence and characteristics of PPOU in opioid-naïve, occasional, and regular opioid users at baseline and at six weeks, three months, and six months postoperatively. METHODS: We conducted a prospective observational study in patients undergoing complex foot and ankle surgery over an 18-month period. Daily opioid consumption was recorded at the indicated intervals. Logistic regression models were fit to predict the risk of opioid use at these intervals. The Brief Pain Inventory (BPI) was used to record pain intensity and interference. Correlations were tested between opioid use and BPI interference parameters. RESULTS: Eighty-two out of 139 consecutively approached patients were included in the final analysis. Six percent (98.3% confidence interval [CI], 2 to 20) of patients who were not using opioids preoperatively at baseline were using opioids daily at three and six months after surgery. Fifty percent (98.3% CI, 26 to 73) of patients who were regular opioid users preoperatively continued to use opioids daily six months after surgery. All associations between BPI interference parameters and opioid use were estimated to be positive. CONCLUSION: The probability of using opioid analgesia six months after complex foot and ankle surgery was significantly higher in patients who used opioids preoperatively. Regular preoperative opioid use was associated with a greater risk of PPOU compared with occasional or "as required" opioid use prior to surgery.

RéSUMé: OBJECTIF: L'incidence de consommation persistante d'opioïdes après une chirurgie (CPOC) après une chirurgie complexe du pied et de la cheville est inconnue. Notre objectif était de déterminer l'incidence et les caractéristiques de la CPOC chez les utilisateurs d'opioïdes naïfs, occasionnels et réguliers avant leur opération, puis à six semaines, trois mois et six mois après l'opération. MéTHODE: Nous avons réalisé une étude observationnelle prospective sur une période de 18 mois auprès de patients bénéficiant d'une chirurgie complexe du pied et de la cheville. La consommation quotidienne d'opioïdes a été enregistrée aux intervalles indiqués. Des modèles de régression logistique ont été utilisés pour prédire le risque de consommation d'opioïdes à ces intervalles. Le Questionnaire concis de la douleur (QCD - version française du Brief Pain Inventory, BPI) a été utilisé pour enregistrer l'intensité de la douleur et son interférence. Des corrélations ont été testées entre la consommation d'opioïdes et les paramètres d'interférence du QCD. RéSULTATS: Quatre-vingt-deux des 139 patients approchés consécutivement ont été inclus dans notre analyse finale. Six pour cent (intervalle de confiance [IC] à 98,3 %, 2 à 20) des patients qui ne consommaient pas d'opioïdes avant l'opération utilisaient des opioïdes quotidiennement trois et six mois après la chirurgie. Cinquante pour cent (IC 98,3 %, 26 à 73) des patients qui étaient des consommateurs réguliers d'opioïdes avant l'opération ont continué à utiliser des opioïdes quotidiennement six mois après la chirurgie. Toutes les associations entre les paramètres d'interférence du QCD et la consommation d'opioïdes ont été estimées positives. CONCLUSION: La probabilité d'avoir recours à une analgésie opioïde six mois après une chirurgie complexe du pied et de la cheville était significativement plus élevée chez les patients qui consommaient déjà des opioïdes avant leur opération. La consommation régulière d'opioïdes avant l'opération a été associée à un risque plus élevé de CPOC par rapport à l'utilisation occasionnelle ou « au besoin ¼ d'opioïdes avant la chirurgie.

Reliable Identification of Endometrial Precancers Through Combined Pax2, ß-Catenin, and Pten Immunohistochemistry.

The diagnosis of endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) remains challenging and subjective in some cases, with variable histologic criteria and differences of opinion among gynecologic pathologists, potentially leading to under/overtreatment. There has been growing interest in the use of specific immunohistochemical markers as adjuncts in AH/EIN diagnosis. For example, the World Health Organization 2020 Classification specifies that loss of Pten, Pax2, or mismatch repair proteins are desirable diagnostic criteria. Other markers, most notably ß-catenin and Arid1a, are also aberrantly expressed in some AH/EIN. However, the performance of some markers individually-and more importantly as a group-has not been rigorously explored, raising questions as to which marker(s) or combination(s) is the most effective in practice. Formalin-fixed paraffin-embedded tissue sections from AH/EIN cases (n=111) were analyzed by immunohistochemistry for 6 markers: Pax2, Pten, Mlh1, ß-catenin, Arid1a, and p53. Aberrant expression was tabulated for each case and marker. An additional set of normal endometria (n=79) was also analyzed to define optimal diagnostic criteria for marker aberrance. The performance characteristics of each marker, the entire panel, and subsets thereof were quantitatively and statistically analyzed. In order of number of cases detected, the most frequently aberrant markers in AH/EIN were Pax2 (81.1% of cases), Pten (50.5%), ß-catenin (47.7%), Arid1a (7.2%), Mlh1 (4.5%), and p53 (2.7%). The majority of cases showed aberrant expression of ≥2 markers. All 6 markers together identified 92.8% of cases. Arid1a, Mlh1, and p53 were robust and readily scored markers, but all cases showing aberrant expression of these 3 markers were also detected by Pax2, Pten, or ß-catenin. A focused panel of only 3 markers (Pax2, Pten, and ß-catenin) showed optimal performance characteristics as a diagnostic adjunct in the histopathologic diagnosis of AH/EIN. Use of this panel is practicable and robust, with at least 1 of the 3 markers being aberrant in 92.8% of AH/EIN.