Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients.

PURPOSE: Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODS AND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method. RESULTS: The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46 years (mean, 48.1 years; range, 10-80 years). The tumor sizes ranged from 0.3 to 6.8 cm, with a mean of 3.5 cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients. CONCLUSION: Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improve diagnosis and management in this unique subtype of breast cancer.

Prognostic factors of 87 ovarian yolk sac tumor (OYST) patients and molecular characteristics of persistent and recurrent OYST.

OBJECTIVE: We aimed to explore the characteristics of OYST, particularly for persistent and recurrent OYST, in order to explore potential treatment options and thereby improve patient outcomes. METHODS: We retrospectively reviewed the clinical records of all patients with OYST at Fudan university Shanghai Cancer Center from December 3, 2005 to November 27, 2020. Furthermore, and performed whole-exome sequencing on 17 paired OYST (including 8 paired persistent and recurrent OYST) tumor and blood samples to elucidate the aberrant molecular features. RESULTS: Totally, 87 OYST patients were included between 2007/03/13 and 2020/11/17. With a median follow-up of 73 [3-189] months, 22 patients relapsed or disease persisted. Overall, 17 patients died with a median overall survival of 21 [3-54] months. Univariate and multivariate analysis revealed tumor histology and residual lesions were independently associated with event free survival and overall survival, cycles to AFP normalization were another independent risk factor for overall survival. For the 8 persistent and recurrent OYST: cancer driver genes including ANKRD36, ANKRD62, DNAH8, MUC5B, NUP205, RYR2, STARD9, MUC16, TTN, ARID1A and PIK3CA were frequently mutated; cell cycle, ABC transporters, HR, NHEJ and AMPK signal pathway demonstrated as the most significantly enriched pathways; TMB, DNA MMR gene mutation and MSI were significantly higher. Mutation signature 11, 19 and 30 were the dominant contributors in persistent and recurrent OYST mutation. CONCLUSION: Persistent and recurrent OYST associated with poor prognosis, and probably susceptible to immune checkpoint blockade therapy. Molecular characteristics contributed to predict the persistence and recurrence of OYST.

Head-to-head comparison of [18F]-FDG and [68 Ga]-DOTA-FAPI-04 PET/CT for radiological evaluation of platinum-sensitive recurrent ovarian cancer.

PURPOSE: Precise radiological evaluation is pivotal for the management of platinum-sensitive recurrent ovarian cancer. We aimed to compare the value of [68 Ga]-FAPI and [18F]-FDG PET/CT for the detection of relapsed lesions. METHODS: Twenty-nine suspected platinum-sensitive recurrent ovarian cancers were enrolled from January 2022 to July 2022. [18F]-FDG and [68 Ga]-FAPI PET/CT were obtained within 1 week for radiological evaluation. Treatment strategies, visual scores, and Eisenkop scores were recorded. A paired T test was used to compare differences between two scans. Sensitivity, specificity, PPV, NPV, and accuracy were also evaluated. RESULTS: Up to 22 (75.86%) patients displayed inconsistency between two scans. Among them, 4 patients with negative [18F]-FDG imaging had measurable lesions in [68 Ga]-FAPI scans. The treatment strategies were changed in 5 patients (17.24%) due to discrepancies. Finally, 15 (35.7%) patients underwent surgeries, and 14 patients achieved complete resection, except for 1 patient who had milliarc residual disease. TBR, but not SUVmax, of [68 Ga]-FAPI was significantly higher than that of [18F]-FDG in recurrent lesions. Compared with [18F]-FDG, [68 Ga]-FAPI PET presented higher sensitivity and accuracy for lesion detection (96.30% vs. 49.07% and 97.40% vs. 63.87%, respectively). Additionally, [68 Ga]-FAPI PET showed a much higher visual score than [18F]-FDG PET (41 vs. 4), especially for peritoneal metastasis (35 vs. 1). [68 Ga]-FAPI PET also presented a larger tumor burden than [18F]-FDG according to the Eisenkop score (27 vs. 16, p = 0.025). CONCLUSIONS: [68 Ga]-FAPI was superior to [18F]-FDG PET/CT for the detection of recurrent lesions, which is pivotal for the individualized management of platinum-sensitive recurrent ovarian cancer.

Diffusion-Weighted Magnetic Resonance Imaging and Morphological Characteristics Evaluation for Outcome Prediction of Primary Debulking Surgery for Advanced High-Grade Serous Ovarian Carcinoma.

BACKGROUND: Preoperative assessment of whether a successful primary debulking surgery (PDS) can be performed in patients with advanced high-grade serous ovarian carcinoma (HGSOC) remains a challenge. A reliable model to precisely predict resectability is highly demanded. PURPOSE: To investigate the value of diffusion-weighted MRI (DW-MRI) combined with morphological characteristics to predict the PDS outcome in advanced HGSOC patients. STUDY TYPE: Prospective. SUBJECTS: A total of 95 consecutive patients with histopathologically confirmed advanced HGSOC (ranged from 39 to 77 years). FIELDS STRENGTH/SEQUENCE: A 3.0 T, readout-segmented echo-planar DWI. ASSESSMENT: The MRI morphological characteristics of the primary ovarian tumor, a peritoneal carcinomatosis index (PCI) derived from DWI (DWI-PCI) and histogram analysis of the primary ovarian tumor and the largest peritoneal carcinomatosis were assessed by three radiologists. Three different models were developed to predict the resectability, including a clinicoradiologic model combing MRI morphological characteristic with ascites and CA125 level; DWI-PCI alone; and a fusion model combining the clinical-morphological information and DWI-PCI. STATISTICAL TESTS: Multivariate logistic regression analyses, receiver operating characteristic (ROC) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI) were used. A P < 0.05 was considered to be statistically significant. RESULTS: Sixty-seven cases appeared as a definite mass, whereas 28 cases as an infiltrative mass. The morphological characteristics and DWI-PCI were independent factors for predicting the resectability, with an AUC of 0.724 and 0.824, respectively. The multivariable predictive model consisted of morphological characteristics, CA-125, and the amount of ascites, with an incremental AUC of 0.818. Combining the application of a clinicoradiologic model and DWI-PCI showed significantly higher AUC of 0.863 than the ones of each of them implemented alone, with a positive NRI and IDI. DATA CONCLUSIONS: The combination of two clinical factors, MRI morphological characteristics and DWI-PCI provide a reliable and valuable paradigm for the noninvasive prediction of the outcome of PDS. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Neoadjuvant chemotherapy followed by radical trachelectomy versus upfront abdominal radical trachelectomy for patients with FIGO 2018 stage IB2 cervical cancer.

OBJECTIVE: To explore the optimal fertility-sparing treatment for stage IB2 cervical cancer. We compared the outcomes of neoadjuvant chemotherapy (NACT) followed by radical trachelectomy (RT) with those of upfront abdominal RT (ART). METHODS: This is a retrospective study with prospectively collected data between August 2015 and July 2019. Patients with IB2 cervical cancer who desired fertility preservation underwent NACT followed by RT, or upfront ART, per their choice. RESULTS: This study included 51 patients, of which, 16 patients underwent NACT followed by RT and 35 patients chose upfront ART. Fertility was preserved in 12 (75.0%) and 27 (77.1%) patients from the NACT and upfront ART groups, respectively. Incidence rates of intraoperative (0% versus 3.7%) and postoperative complications (25.0% versus 48.1%) of the NACT group were lower compared to the upfront ART group (P=NS). Eleven (91.7%) patients in NACT group and 17 (63.0%) patients in upfront ART groups received adjuvant chemotherapy after surgery. The median follow-up, and 5-year recurrence-free survival rates of the NACT-RT and upfront ART groups were 56 and 61 months, and 83.3% and 96.3%, respectively (P=NS). The recurrence rate was higher in patients with tumor reduction <50% after NACT than that in patients with tumor reduction >50% (66.7% versus 0%, P < 0.05). Tumor reduction <50% was the only independent predictor of recurrence in patients who underwent NACT before RT. CONCLUSIONS: NACT followed by RT could be a feasible fertility-sparing option for selected patients with 1B2 cervical cancer. The NACT group had a relatively higher recurrence rate and fewer complications compared to the upfront ART group, albeit without statistical significance. Patients with tumor regression >50% after NACT could be ideal candidates for RT after NACT.

Release of Leu-Pro-Pro from corn gluten meal by fermentation with a Lactobacillus helveticus strain.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitory peptides are potential alternatives to the synthetic ACE inhibitory drugs, but the in vivo antihypertensive effects of most of them have not been confirmed. The tripeptide Leu-Pro-Pro (LPP) is one of the few peptides that have been proved clinically effective in reducing the blood pressure of hypertensive patients and casein is currently its major source. LPP is contained in multiple fractions of zein, and corn gluten meal (CGM) is hence a potential new source of LPP. For this purpose, CGM was fermented with a Lactobacillus helveticus strain and the medium composition was optimized; the decoloration of the resultant hydrolysate was investigated as well. RESULTS: LPP could be successfully released from CGM by fermentation with the strain Lactobacillus helveticus CICC 22536. The highest LPP content and protein recovery of 561 mg kg-1 and 14.92% occurred in the medium containing 20 g L-1 glucose, 15 g L-1 beef extract, 60 g L-1 CGM, 10 g L-1 CaCO3 , 0.5 g L-1 NaCl, and inoculation amount 6%. The supplementation of Flavourzyme® further improved the two parameters to 662 mg kg-1 and 36.94%, respectively. The permeate of the hydrolysate after ultrafiltration through a 5 kDa membrane could be effectively decolored by the macroporous resin XAD-16 without notable protein loss, and its LPP content was further boosted to 743 mg kg-1 . CONCLUSION: CGM is a potential new source of LPP and its ultrafiltered and decolored hydrolysate could be used to develop new antihypertensive functional foods. © 2021 Society of Chemical Industry.

Haplotype-based approach for noninvasive prenatal tests of Duchenne muscular dystrophy using cell-free fetal DNA in maternal plasma.

PURPOSE: This study demonstrates noninvasive prenatal testing (NIPT) for Duchenne muscular dystrophy (DMD) using a newly developed haplotype-based approach. METHODS: Eight families at risk for DMD were recruited for this study. Parental haplotypes were constructed using target-region sequencing data from the parents and the probands. Fetal haplotypes were constructed using a hidden Markov model through maternal plasma DNA sequencing. The presence of haplotypes linked to the maternal mutant alleles in males indicated affected fetuses. This method was further validated by comparing the inferred single-nucleotide polymorphism (SNP) genotypes to the direct sequencing results of fetal genomic DNA. Prenatal diagnosis was confirmed with amniocentesis, and those results were interpreted in a blinded fashion. RESULTS: The results showed an average accuracy of 99.98% for the total inferred maternal SNPs. With a mean depth of 30× achieved in the 10-Mb target region of each sample, the noninvasive results were consistent with those of the invasive procedure. CONCLUSION: This is the first report of NIPT for DMD and the first application of a haplotype-based approach in NIPT for X-linked diseases. With further improvements in accuracy, this haplotype-based strategy could be feasible for NIPT for DMD and even other X-linked single-gene disorders.

Primer-introduced restriction analysis polymerase chain reaction method for non-invasive prenatal testing of ß-thalassemia.

We have developed a new method for non-invasive prenatal testing (NIPT) of paternally inherited fetal mutants for ß-thalassemia (ß-thal). Specially designed primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) were used to detect four major mutations [IVS-II-654, HBB: c.316-197C > T; codon 17 (A > T), HBB: c.52A > T; -28 (A > G), HBB: c.-78A > G and codons 41/42 (-TTCT), HBB: c.126_129delCTTT] causing ß-thal in China. The PIRA-PCR assay was first tested in a series of mixed DNA with different concentrations and mixed proportions. Subsequently, this assay was further tested in 10 plasma DNA samples collected from pregnant women. In the DNA mixture simulation test, the PIRA-PCR assay was able to detect 3.0% target genomic DNA (gDNA) mixed in 97.0% wild-type gDNA isolated from whole blood. For plasma DNA testing, the results detected by PIRA-PCR assay achieved 100.0% consistency with those obtained from the amniocentesis analysis. This new method could potentially be used for NIPT of paternally inherited fetal mutants for ß-thal.

Integration of targeted sequencing and NIPT into clinical practice in a Chinese family with maple syrup urine disease.

PURPOSE: This article demonstrates a prominent noninvasive prenatal approach to assist the clinical diagnosis of a single-gene disorder disease, maple syrup urine disease, using targeted sequencing knowledge from the affected family. METHODS: The method reported here combines novel mutant discovery in known genes by targeted massively parallel sequencing with noninvasive prenatal testing. RESULTS: By applying this new strategy, we successfully revealed novel mutations in the gene BCKDHA (Ex2_4dup and c.392A>G) in this Chinese family and developed a prenatal haplotype-assisted approach to noninvasively detect the genotype of the fetus (transmitted from both parents). CONCLUSION: This is the first report of integration of targeted sequencing and noninvasive prenatal testing into clinical practice. Our study has demonstrated that this massively parallel sequencing-based strategy can potentially be used for single-gene disorder diagnosis in the future.

Noninvasive prenatal testing for autosomal recessive conditions by maternal plasma sequencing in a case of congenital deafness.

PURPOSE: The goals of our study were to develop a noninvasive prenatal test for autosomal recessive monogenic conditions and to prove its overall feasibility and potential for clinical integration. METHODS: We recruited a pregnant woman and her spouse, who had a proband child suffering from congenital deafness, and obtained the target-region sequencing data from a semicustom array that used genomic and maternal plasma DNA from three generations of this family. A haplotype-assisted strategy was developed to detect whether the fetus inherited the pathogenic mutations in the causative gene, GJB2. The parental haplotype was constructed using a trio strategy through two different processes, namely, the grandparent-assisted haplotype phasing process and the proband-assisted haplotype phasing process. The fetal haplotype was deduced afterward based on both the maternal plasma sequencing data and the parental haplotype. RESULTS: The accuracy levels of paternal and maternal haplotypes obtained by grandparent-assisted haplotype phasing were 99.01 and 97.36%, respectively, and the proband-assisted haplotype phasing process yielded slightly lower accuracies of 98.73 and 96.79%, respectively. Fetal inheritance of the pathogenic gene was deduced correctly in both processes. CONCLUSION: Our study indicates that the strategy of haplotype-based noninvasive prenatal testing for monogenic conditions has potential applications in clinical practice.

Surgical and pathological outcomes of abdominal radical trachelectomy versus hysterectomy for early-stage cervical cancer.

OBJECTIVES: The aim of this study was to compare the surgical and pathological outcomes for patients with early-stage cervical cancer after abdominal radical trachelectomy (ART) and abdominal radical hysterectomy (ARH). METHODS: A prospective database of ART and ARH procedures performed in a standardized manner by the same surgical group was analyzed. The 3-segment technique was used for the accurate analysis of parametrial lymph nodes (PMLNs), and parametrial measurements were recorded by the same pathologist. Standard statistical tests were used. RESULT: Between August 2012 and August 2013, ART was attempted in 39 patients (28.6%), and ARH was attempted in 90 patients (71.4%). The parametrium resection length was similar with ART and ARH (44.60 vs 45.48 mm, P = 0.432), as were additional surgical and pathological outcomes, including histology, lymph node positive rate, and operation time. The PMLNs were found in 28 patients (77.78%) in the ART group and in 86 (95.56%) in the ARH group (P > 0.05). Solitary PMLN metastases were observed in 3 patients (10.71%) in the ART group and in 6 (6.98%) in the ARH group. Five (55.6%) of these 9 patients had tumors of 2 cm or greater. The ARH patients (36, 40.00%) were more likely to receive postoperative chemotherapy or radiation compared with ART patients (13, 33.33%; P = 0.017). At a median follow-up of 12 and 12.5 months (P = 0.063), respectively, there were no recurrences or deaths in the ART or ARH groups. CONCLUSIONS: Using standardized techniques, ART provides similar surgical and pathological outcomes as ARH. For the patients with tumors of 2 cm or greater, PMLNs should be examined carefully. Further prospective data are urgently needed.

Noninvasive prenatal testing of trisomies 21 and 18 by massively parallel sequencing of maternal plasma DNA in twin pregnancies.

OBJECTIVE: The objective of this study is to assess the performance of noninvasive prenatal testing for trisomies 21 and 18 on the basis of massively parallel sequencing of cell-free DNA from maternal plasma in twin pregnancies. METHOD: A double-blind study was performed over 12 months. A total of 189 pregnant women carrying twins were recruited from seven hospitals. Maternal plasma DNA sequencing was performed to detect trisomies 21 and 18. The fetal karyotype was used as gold standard to estimate the sensitivity and specificity of sequencing-based noninvasive prenatal test. RESULTS: There were nine cases of trisomy 21 and two cases of trisomy 18 confirmed by karyotyping. Plasma DNA sequencing correctly identified nine cases of trisomy 21 and one case of trisomy 18. The discordant case of trisomy 18 was an unusual case of monozygotic twin with discordant fetal karyotype (one normal and the other trisomy 18). The sensitivity and specificity of maternal plasma DNA sequencing for fetal trisomy 21 were both 100% and for fetal trisomy 18 were 50% and 100%, respectively. CONCLUSION: Our study further supported that sequencing-based noninvasive prenatal testing of trisomy 21 in twin pregnancies could be achieved with a high accuracy, which could effectively avoid almost 95% of invasive prenatal diagnosis procedures.

Uterine Tumor Resembling Ovarian Sex Cord Tumors: 23 Cases Indicating Molecular Heterogeneity With Variable Biological Behavior.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm that mainly harbors NCOA1-3 rearrangements with partner genes ESR1 or GREB1 . Here, we explored 23 UTROSCTs by targeted RNA sequencing. The association between molecular diversity and clinicopathologic features was investigated. The mean age of our cohort was 43 years (23-65 y). Only 15 patients (65%) were originally diagnosed with UTROSCTs. Mitotic figures ranged from 1 to 7/10 high power fields, of primary tumors and increased from 1 to 9/10 high power fields in recurrent tumors. Five types of gene fusions were identified in these patients, including GREB1::NCOA2 (n=7), GREB1::NCOA1 (n=5), ESR1::NCOA2 (n=3), ESR1::NCOA3 (n=7), and GTF2A1::NCOA2 (n=1). To our knowledge, our group included the largest cohort of tumors with GREB1::NCOA2 fusions. Recurrences were most common in patients with GREB1::NCOA2 fusion (57%), followed by 40% ( GREB1::NCOA1 ), 33% ( ESR1::NCOA2 ), and 14% ( ESR1::NCOA3 ). The recurrent patient who harbored an ESR1::NCOA2 fusion was characterized by extensive rhabdoid features. Both of the recurrent patients who harbored GREB1::NCOA1 and ESR1::NCOA3 had the largest tumor sizes in their own gene alteration groups, and another recurrent GREB1::NCOA1 patient had extrauterine involvement. The GREB1 -rearranged patients were of older age, larger tumor size, and higher stage than non- GREB1 -rearranged patients ( P =0.004, 0.028, and 0.016, respectively). In addition, the GREB1 -rearranged tumors presented more commonly as intramural masses rather than non- GREB1 -rearranged tumors presenting as polypoid/submucosal masses ( P =0.021). Microscopically, nested and whorled patterns were frequently seen in GREB1- rearranged patients ( P =0.006). Of note, estrogen receptor expression was weaker than progesterone receptor in all 12 GREB1- rearranged tumors, whereas the similar staining intensity of estrogen receptor and progesterone receptor was observed in all 11 non- GREB1- rearranged tumors ( P <0.0001). This study demonstrated that UTROSCTs were present at a younger age in the Chinese population. The genetic heterogeneity of UTROSCTs was correlated with variable recurrence rate. Tumors with GREB1::NCOA2 fusions are more likely to recur compared with those with other genetic alterations.

Comprehensive quantitative malignant risk prediction of pure grouped amorphous calcifications: clinico-mammographic nomogram.

Background: Pure grouped amorphous calcifications are classified as Breast Imaging Reporting and Data System (BI-RADS) category 4B suspicious calcifications and recommended for biopsy. However, the biopsies often reveal benign findings, especially in screening mammograms (92.4-97.2%). Methods: Mammograms of 699 pure grouped amorphous calcifications with final pathological results were analyzed in this retrospective study. The maximum span (MS) of the group of calcifications and the MS of the parallel/vertical direction of the mammary duct (MPS/MVS) were measured, and the MPS to MVS ratio was calculated. Based on the MS and ratio, 2 prediction nomograms with other clinic-mammographic features were developed. The discrimination performance of the models was assessed and compared by the area under the receiver operating characteristic curve (AUC). Scatterplots were created to determine the cutoff values with fewer misdiagnoses of malignant calcifications and fewer false positives. Results: Ultimately, 2 prediction models were successfully developed based on the 4 risk factors of age, purpose of the mammogram, whether multiple or single calcifications, and the MS [odds ratio (OR) =1.06, P=0.02]/ratio (OR =6.05, P<0.001). Both models had good discrimination. The ratio model performed better than the MS model in the training cohort (AUC of 0.875 and 0.834, respectively, P=0.003) and validation cohort (AUC 0.908 and 0.867, respectively, P=0.047). For the group with probably benign calcifications (as detected by the ratio nomogram), the malignancy rates were 2.7% [95% confidence interval (CI): 1.00% to 6.53%] and 1.19% (95% CI: 0.06% to 7.37%) in the training and validation cohorts, respectively, and 44.12% and 47.70% of benign biopsies were detected in the training and validation cohorts, respectively. Conclusions: The clinico-mammographic quantitative malignancy risk prediction nomogram showed favorable discrimination and calibration performance. The ratio model showed better diagnostic efficiency than the MS model, and identified >40% of benign biopsies.

Clinicopathological and molecular characteristics of fumarate hydratase-deficient uterine smooth muscle tumors: a single-center study of 52 cases.

The fumarate hydratase (FH) gene germline mutations cause hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC), predisposing carriers to uterine and cutaneous leiomyomas and renal cell carcinoma. In this study, we aim to investigate morphology and the correlation between FH mutation in FH-deficient (FH-d) uterine smooth muscle tumors (uSMTs). We conducted immunohistochemical staining in 161 cases of uSMTs to detect FH deficiency. We identified 52 cases (52/161, 32%) of FH-d, including 34 leiomyomas with bizarre nuclei, 10 uSMTs of uncertain malignant potential (STUMPs), 4 cellular leiomyomas, 3 usual type leiomyomas, and 1 leiomyosarcoma. Patients with FH-d were aged 24-67 years (median, 40 years). The most common FH-d morphological features included staghorn-shaped blood vessels (87%), bizarre nuclei (81%), alveolar pattern edema (65%), macronucleoli surrounded by a halo (65%), cytoplasmic eosinophilic globules (56%), and chain-like distribution of smooth muscle cells (52%). A targeted next-generation sequence was performed in 11 of 52 FH-d tumors. Five cases (5/11, 45%) were found with FH germline mutations, including 4 leiomyomas with bizarre nuclei and 1 STUMP. The median age of patients with germline FH mutation was 30 years. The germline mutations included 3 pathogenic, 1 likely pathogenic, and 1 rare uncertain clinical significance variants. Our results revealed that FH-d uSMTs usually exhibit the distinct morphology features and high frequency of FH germline mutations. The combination of predictive morphology evaluation, FH immunotype, and molecular testing is helpful for the screening of HLRCC in uSMTs.

Pure primary yolk sac tumor of the endometrium tends to occur at a younger age: A case report and literature analysis.

We present a case of primary yolk sac tumor of the endometrium. This rare tumor occurred in a 43-year-old woman with a pure primary yolk sac tumor. The tumor resembled yolk sac tumor morphology of the ovary. Tumor cells expressed SALL4, AFP, GPC-3, and AE1/AE3 and were focal positive for PAX8. EMA, ER, and PR, among others, were negative. We further analyzed 29 reported cases of this rare tumor in the literature. In total, 17 of 30 patients (57%) had pure endometrial yolk sac tumor, and 13 (43%) had a concomitant somatic neoplasm (endometrial adenocarcinoma was the most common). Although the average age was 52 years (range: 24-87 years), patients with pure yolk sac tumor were younger than those with concomitant somatic tumors, with a mean age of 44.41 years (24-68 years) versus 61.92 years (28-87 years), P = 0.008. Patients with endometrial yolk sac tumor combined with somatic tumor tend to have a slightly higher stage and a poor prognosis.

Prognostic and predictive values of the KIT11-mutated grading system in patients with gastrointestinal stromal tumors: a retrospective study.

The KIT11 mutation is the most frequent mutation pattern in gastrointestinal stromal tumors (GISTs). However, few studies have investigated the correlation between the KIT11-mutated grading system and imatinib mesylate (IM) sensitivity (the first choice for adjuvant treatment of GISTs). Here, we elucidated the clinical value of the KIT11-mutated grading system for prognostic prediction in patients with GISTs treated with IM. A total of 106 patients with GIST were treated with IM (8: intermediate-risk, 98: high-risk; 10: KIT9-mutated, 86: KIT11-mutated, 5: wild-type, and 5: other mutations). KIT11-mutated patients were divided into 3 grades based on the KIT11-mutated site and type. Clinical backgrounds and prognostic outcomes were retrospectively compared between the 3 groups. Of 86 KIT11-mutated patients treated with IM, 32 (37.21%) had grade 1 tumors, 37 (43.02%) had grade 2 tumors, and 17 (19.77%) had grade 3 tumors. The 5-year disease-free survival (DFS) was significantly worse in patients with grade 3 KIT11-mutated GISTs (41.96%, p = 0.001) than in those with grade 1 (93%) and grade 2 (70.64%) cases. The multivariable analysis suggested that the KIT11-mutated grading system was an independent risk factor for DFS in patients treated with IM (hazard risk, 2.512; 95% confidence interval, 1.370-4.607; p = 0.003). In conclusion, the KIT11-mutated grading system provides good prognostic stratification for DFS in patients treated with IM. Grade 1 tumors predict a favorable response to IM.

A novel 2-deoxy-2-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT)-based nomogram to predict lymph node metastasis in early stage uterine cervical squamous cell cancer.

BACKGROUND: We aimed to establish an effective 2-deoxy-2-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) based nomogram for pelvic lymph node (PLN) metastasis prediction in early-stage uterine cervical squamous cell cancer. METHODS: A predictive model was developed in a cohort that consisted of 351 patients with stage IB-IIA [International Federation of Gynecology and Obstetrics (FIGO) 2009] uterine cervical squamous cell cancer. All patients underwent a preoperative PET/CT scan and subsequent radical surgery between 2010 and 2017, with 241 and 110 patients allotted into training and external validation cohorts. The chi-square (χ2) test and the logistic regression analysis were used to compare the clinical and PET/CT parameters with PLN metastasis. A nomogram was developed and validated by internal and external validation. RESULTS: In the training cohort, 82 (34.0%) patients had positive PLNs identified in the preoperative PET/CT scan. Among them, 46 (56.1%) were pathologically confirmed. There were 30 (18.9%) PET/CT scan-negative patients found to have PLN metastasis. The χ2 test and logistic regression showed that only the squamous cell carcinoma antigen (SCCA) level (P=0.039) and maximum standardized uptake value (SUVmax) of PLN (nSUVmax, P=0.001) were independent predictors for PLN metastasis. A predictive nomogram based on these 2 parameters was developed with a C-index [95% confidence interval (CI)] of 0.854 (0.772-0.937) on internal validation and 0.836 (0.723-0.948) on the external validation. Compared to nSUVmax alone, our nomogram showed elevated sensitivity (70.5%, 73.1% vs. 60.5%), specificity (94.4%, 86.4% vs. 78.2%), and positive predictive value (PPV) (93.9%, 86.4% vs. 56.1%) in both the training and validation cohorts. CONCLUSIONS: We successfully developed a noninvasive and convenient nomogram for preoperative identification of PLN metastasis in early-stage squamous cell cervical cancer.

Mismatch repair deficiency is associated with specific morphologic features and frequent loss of ARID1A expression in ovarian clear cell carcinoma.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is the second subtype of ovarian epithelial carcinoma reported to be closely related to Lynch syndrome (LS). ARID1A mutation is an important pathogenetic mechanism in OCCC that leads to loss of ARID1A expression in approximately half of OCCCs. However, the correlation of MMR status and ARID1A deficiency is unclear. The current study aimed to identify the clinical and histopathological characteristics of OCCC associated with dMMR and to further explore the association between dMMR and ARID1A deficiency. METHODS: A cohort of 176 primary OCCC patients was enrolled and review included histological characteristics (nuclear atypia, necrosis, mitosis, stromal hyalinization, and background precursors) and host inflammatory response (tumor-infiltrating lymphocytes, peritumoral lymphocytes, intratumoral stromal inflammation and plasma cell infiltration). Immunohistochemical staining of MLH1, PMS2, MSH2, MSH6 and ARID1A was performed using tissue microarrays. RESULTS: dMMR was detected in 10/176 tumors (6 %), followed by MSH2/MSH6 (6/176), MLH1/PMS2 (3/176), and MSH6 (1/176). The average age of patients with dMMR was younger than that of patients with intact MMR (46 y vs. 53 y). Tumors with diffuse intratumoral stromal inflammation remained significantly associated after multivariate analysis. ARID1A expression was absent in 8 patients with dMMR (8/10), which is a significantly higher frequency than that observed in patients with intact MMR (80 % vs. 43.2 %). CONCLUSIONS: Our study indicates that diffuse intratumoral stromal inflammation of OCCCs is associated with dMMR, with loss of MSH2/MSH6 expression being most frequent. dMMR is strongly associated with the loss of ARID1A expression in OCCC.

Preoperative PET/CT score can predict complete resection in advanced epithelial ovarian cancer: a prospective study.

BACKGROUND: To assess the ability of preoperative positron emission tomography/computed tomography (PET/CT) scans to predict postoperative residual disease in advanced epithelial ovarian cancer (AEOC). METHODS: Thirty-one women with suspected AEOC were enrolled in our prospective study before surgery from July 2016 to December 2017. Complete resection was determined as no residual disease (R0) after surgery. A PET/CT scan was obtained within 2 weeks before surgery in our hospital. The PET score was the sum of each score of the radiological criteria from Suidan's model. The correlations between the PET score and tumor burden and surgical complexity were evaluated by Pearson correlation analysis. T-test or Fisher's exact test was used to compare differences in the variables between the complete and incomplete resection groups. Receiver operating characteristic (ROC) curve analysis was performed to assess the accuracy of the PET score for predicting complete postoperative resection. RESULTS: The median [range] of PET score was 2 [0-8], and the PET score in 20 (65%) patients was less than 3. Complete resection was achieved in 11 (35.5%) patients after surgery, including 10 (90.91%) with low PET scores and only 1 (9.09%) with a high score. The PET score had a significant positive correlation with tumor burden [Eisenkop: r=0.603, P<0.001; peritoneal cancer index (PCI): r=0.522, P=0.003] but not with surgery complexity (Aletti: r=0.291, P=0.113). Patients with lower PET scores (P=0.046) and tumor burdens (Eisenkop: P=0.013; PCI: P=0.012) had higher rates of complete resection. The PET score and tumor burden were effective for predicting complete resection. The AUCPET, AUCEisenkop, and AUCPCI were 0.797 (95% CI: 0.633-0.961, P=0.01), 0.847 (95% CI: 0.707-0.988, P=0.003), and 0.811 (95% CI: 0.653-0.969, P=0.007), respectively. However, surgery complexity was not useful for assessing complete resection. CONCLUSIONS: The preoperative PET score can noninvasively reflect tumor burden and helps predict complete resection after surgery in AEOC patients.