Objective:To investigate the cytopathological features of thyroid tumor with DICER1 mutation.Methods:A retrospective study on the preoperative cell smear was conducted on thyroid tumors with DICER1 gene mutations detected by Sanger sequencing in the Department of Pathology Shanghai Sixth People′s Hospital affiliated to Shanghai Jiaotong University School of Medicine from May 2022 to November 2024.Results:Totally 163 cases with histological features indicating DICER1 mutation related thyroid tumor underwent Sanger sequencing. Fifteen cases were confirmed to harbor DICER1 mutation (15/163,9.2%). Fourteen of 15 patients were female, and only 1 was male; average age 42(31,47) years. Eight cases presented with D1709 hotspot mutation (8/15) and 7 cases with the E1813 hotspot mutation (7/15) and there was no statistical significant difference between mutation rate of different hotspot ( F=0.620， P=0.438). All specimens were stained with hematoxylin-eosin staining. A moderate number of cells were observed for all cases, predominantly with macrofollicular pattern and rare small papillae. The cell nuclei were mainly uniform, small, round and dark, slightly enlarged or medium-sized. Several cases could also present RAS-like nuclear features: 3 cases showed visible nuclear grooves. According to the expert consensus on the cytopathological diagnosis of thyroid fine needle aspiration (version 2023),the cytopathological diagnostic categories were: Ⅱ, 6 cases; Ⅲ, 2 cases; Ⅳ, 6 cases; and Ⅴ, 1 case. Postoperative histological diagnoses included follicular thyroid carcinoma in 2 cases, high-grade differentiated thyroid carcinoma in 1 case, follicular thyroid adenoma in 3 cases, follicular thyroid tumor of undetermined malignant potential in 4 case, and thyroid follicular nodular disease in 5 cases. Conclusions:The morphological features of DICER1-mutated thyroid tumors are predominant macrofollicles, with uniformly small round and dark nuclei. It is difficult to identify typically diagnostic atrophic follicles on cell smear, leading to a preoperative diagnosis of benign non-neoplastic or indeterminate category. Therefore, it is necessary to carefully observe the macro-follicles and small round dark nuclear features, which is necessary to suggest a genetic test of DICER1 gene and to confirm the diagnosis before surgery.

Objective:To analyze the cytological, histological, immunohistochemical, and molecular pathological features of hyalinizing trabecular tumor (HTT).Methods:Clinical and pathological data of the HTT cases diagnosed at Shanghai Sixth People′s Hospital affiliated to Shanghai Jiao Tong University School of Medicine between 2020 and 2024 were collected and analyzed. HE staining, special staining, immunohistochemical staining, and next-generation sequencing were performed on all cases.Results:Among the 10 HTT patients, 4 were male and 6 were female. The age at onset ranged from 29 to 85 years, with a median age of 49 (35,61) years. The maximum tumor diameter ranged from 0.3 to 5.3 cm. Cytologically, the smears were hypercellular and showed tumor cells arranged in nested clusters with visible basement membrane-like material. The nuclei were oval with finely granular chromatin, and nuclear pseudoinclusions were readily identifiable. Histologically, the tumors were well demarcated. The tumor cells were arranged in a paraganglioma-like pattern, exhibiting typical nuclear features of papillary thyroid carcinoma and psammoma bodies. Yellow bodies were observed in the cytoplasm. The stroma was rich in hyalinized material, which was periodic acid-Schiff stain (PAS)-positive. Immunohistochemically, the tumor cells showed diffuse expression of TTF-1 and focal expression of thyroglobulin. Aberrant immunoreaction with Ki-67 was present in the cytoplasm and membrane of the tumor cells. Molecular testing was performed on 8 cases. The PAX8-GLIS3 gene fusion was detected in 7 cases. Among these fusion-positive cases, 4 exhibited additional genetic abnormalities: one concurrent TSHR point mutation (p.D617H); one concurrent HRAS point mutation (p.Q61R); one concurrent LRP1B point mutation (p.S1752L), SUGCT point mutation (p.K137), and TERT point mutation (p.P785L); one concurrent MTOR mutation (7528+27A>T) and FLT3 mutation (p.E77K). The key initiating factors for thyroid carcinoma, including the BRAF V600E mutation and RET rearrangements, were absent in all cases tested.Conclusions:Cellular pleomorphism, yellow bodies and basement membrane-like material constitute important cytological and histological features for the differential diagnosis of HTT. Immunophenotypically, thyroglobulin may show focal expression, while Ki-67 is typically localized in the tumor cell membrane and cytoplasm. This study also demonstrates that PAX8-GLIS3 fusion is a characteristic molecular abnormality in HTT, although cases with wild type of GLIS gene may also present. Although rare, HTT may harbor point mutations in HRAS and TSHR, and other uncommon genetic alterations.

Objective:To investigate the cytopathological features of thyroid tumor with DICER1 mutation.Methods:A retrospective study on the preoperative cell smear was conducted on thyroid tumors with DICER1 gene mutations detected by Sanger sequencing in the Department of Pathology Shanghai Sixth People′s Hospital affiliated to Shanghai Jiaotong University School of Medicine from May 2022 to November 2024.Results:Totally 163 cases with histological features indicating DICER1 mutation related thyroid tumor underwent Sanger sequencing. Fifteen cases were confirmed to harbor DICER1 mutation (15/163,9.2%). Fourteen of 15 patients were female, and only 1 was male; average age 42(31,47) years. Eight cases presented with D1709 hotspot mutation (8/15) and 7 cases with the E1813 hotspot mutation (7/15) and there was no statistical significant difference between mutation rate of different hotspot ( F=0.620， P=0.438). All specimens were stained with hematoxylin-eosin staining. A moderate number of cells were observed for all cases, predominantly with macrofollicular pattern and rare small papillae. The cell nuclei were mainly uniform, small, round and dark, slightly enlarged or medium-sized. Several cases could also present RAS-like nuclear features: 3 cases showed visible nuclear grooves. According to the expert consensus on the cytopathological diagnosis of thyroid fine needle aspiration (version 2023),the cytopathological diagnostic categories were: Ⅱ, 6 cases; Ⅲ, 2 cases; Ⅳ, 6 cases; and Ⅴ, 1 case. Postoperative histological diagnoses included follicular thyroid carcinoma in 2 cases, high-grade differentiated thyroid carcinoma in 1 case, follicular thyroid adenoma in 3 cases, follicular thyroid tumor of undetermined malignant potential in 4 case, and thyroid follicular nodular disease in 5 cases. Conclusions:The morphological features of DICER1-mutated thyroid tumors are predominant macrofollicles, with uniformly small round and dark nuclei. It is difficult to identify typically diagnostic atrophic follicles on cell smear, leading to a preoperative diagnosis of benign non-neoplastic or indeterminate category. Therefore, it is necessary to carefully observe the macro-follicles and small round dark nuclear features, which is necessary to suggest a genetic test of DICER1 gene and to confirm the diagnosis before surgery.

Objective:To analyze the cytological, histological, immunohistochemical, and molecular pathological features of hyalinizing trabecular tumor (HTT).Methods:Clinical and pathological data of the HTT cases diagnosed at Shanghai Sixth People′s Hospital affiliated to Shanghai Jiao Tong University School of Medicine between 2020 and 2024 were collected and analyzed. HE staining, special staining, immunohistochemical staining, and next-generation sequencing were performed on all cases.Results:Among the 10 HTT patients, 4 were male and 6 were female. The age at onset ranged from 29 to 85 years, with a median age of 49 (35,61) years. The maximum tumor diameter ranged from 0.3 to 5.3 cm. Cytologically, the smears were hypercellular and showed tumor cells arranged in nested clusters with visible basement membrane-like material. The nuclei were oval with finely granular chromatin, and nuclear pseudoinclusions were readily identifiable. Histologically, the tumors were well demarcated. The tumor cells were arranged in a paraganglioma-like pattern, exhibiting typical nuclear features of papillary thyroid carcinoma and psammoma bodies. Yellow bodies were observed in the cytoplasm. The stroma was rich in hyalinized material, which was periodic acid-Schiff stain (PAS)-positive. Immunohistochemically, the tumor cells showed diffuse expression of TTF-1 and focal expression of thyroglobulin. Aberrant immunoreaction with Ki-67 was present in the cytoplasm and membrane of the tumor cells. Molecular testing was performed on 8 cases. The PAX8-GLIS3 gene fusion was detected in 7 cases. Among these fusion-positive cases, 4 exhibited additional genetic abnormalities: one concurrent TSHR point mutation (p.D617H); one concurrent HRAS point mutation (p.Q61R); one concurrent LRP1B point mutation (p.S1752L), SUGCT point mutation (p.K137), and TERT point mutation (p.P785L); one concurrent MTOR mutation (7528+27A>T) and FLT3 mutation (p.E77K). The key initiating factors for thyroid carcinoma, including the BRAF V600E mutation and RET rearrangements, were absent in all cases tested.Conclusions:Cellular pleomorphism, yellow bodies and basement membrane-like material constitute important cytological and histological features for the differential diagnosis of HTT. Immunophenotypically, thyroglobulin may show focal expression, while Ki-67 is typically localized in the tumor cell membrane and cytoplasm. This study also demonstrates that PAX8-GLIS3 fusion is a characteristic molecular abnormality in HTT, although cases with wild type of GLIS gene may also present. Although rare, HTT may harbor point mutations in HRAS and TSHR, and other uncommon genetic alterations.

This study was designed to compare diagnostic categories of thyroid fine needle aspiration cytology (FNAC) and incidence of thyroid tumors in the multi-institutional Asian series with a special focus on diagnostic category IV (suspicious for a follicular neoplasm) and follicular thyroid carcinomas (FTCs). Methods: Distribution of FNAC categories, incidence of thyroid tumors in resection specimens and cytologic diagnoses of surgically confirmed follicular adenomas (FAs) and FTCs were collected from 10 institutes from five Asian countries and were compared among countries and between FAs and FTCs. Results: The frequency of category IV diagnoses (3.0%) in preoperative FNAC were significantly lower compared to those in Western countries (10.1%). When comparing diagnostic categories among Asian countries, category IV was more frequent in Japan (4.6%) and India (7.9%) than in Taiwan (1.4%), Korea (1.4%), and China (3.6%). Similarly, incidence of FAs and FTCs in surgical resection specimens was significantly higher in Japan (10.9%) and India (10.1%) than in Taiwan (5.5%), Korea (3.0%), and China (2.5%). FTCs were more commonly diagnosed as category IV in Japan (77.5%) than in Korea (33.3%) and China (35.0%). Nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were more common in FTCs compared with FAs. Conclusions: Our study highlighted the difference in FNAC diagnostic categories of FTCs among Asian countries, which is likely related to different reporting systems and thyroid cancer incidence. Cytologic features such as nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were found to be useful in diagnosing FTCs more effectively.

This study was designed to compare diagnostic categories of thyroid fine needle aspiration cytology (FNAC) and incidence of thyroid tumors in the multi-institutional Asian series with a special focus on diagnostic category IV (suspicious for a follicular neoplasm) and follicular thyroid carcinomas (FTCs). Methods: Distribution of FNAC categories, incidence of thyroid tumors in resection specimens and cytologic diagnoses of surgically confirmed follicular adenomas (FAs) and FTCs were collected from 10 institutes from five Asian countries and were compared among countries and between FAs and FTCs. Results: The frequency of category IV diagnoses (3.0%) in preoperative FNAC were significantly lower compared to those in Western countries (10.1%). When comparing diagnostic categories among Asian countries, category IV was more frequent in Japan (4.6%) and India (7.9%) than in Taiwan (1.4%), Korea (1.4%), and China (3.6%). Similarly, incidence of FAs and FTCs in surgical resection specimens was significantly higher in Japan (10.9%) and India (10.1%) than in Taiwan (5.5%), Korea (3.0%), and China (2.5%). FTCs were more commonly diagnosed as category IV in Japan (77.5%) than in Korea (33.3%) and China (35.0%). Nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were more common in FTCs compared with FAs. Conclusions: Our study highlighted the difference in FNAC diagnostic categories of FTCs among Asian countries, which is likely related to different reporting systems and thyroid cancer incidence. Cytologic features such as nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were found to be useful in diagnosing FTCs more effectively.

This study was designed to compare diagnostic categories of thyroid fine needle aspiration cytology (FNAC) and incidence of thyroid tumors in the multi-institutional Asian series with a special focus on diagnostic category IV (suspicious for a follicular neoplasm) and follicular thyroid carcinomas (FTCs). Methods: Distribution of FNAC categories, incidence of thyroid tumors in resection specimens and cytologic diagnoses of surgically confirmed follicular adenomas (FAs) and FTCs were collected from 10 institutes from five Asian countries and were compared among countries and between FAs and FTCs. Results: The frequency of category IV diagnoses (3.0%) in preoperative FNAC were significantly lower compared to those in Western countries (10.1%). When comparing diagnostic categories among Asian countries, category IV was more frequent in Japan (4.6%) and India (7.9%) than in Taiwan (1.4%), Korea (1.4%), and China (3.6%). Similarly, incidence of FAs and FTCs in surgical resection specimens was significantly higher in Japan (10.9%) and India (10.1%) than in Taiwan (5.5%), Korea (3.0%), and China (2.5%). FTCs were more commonly diagnosed as category IV in Japan (77.5%) than in Korea (33.3%) and China (35.0%). Nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were more common in FTCs compared with FAs. Conclusions: Our study highlighted the difference in FNAC diagnostic categories of FTCs among Asian countries, which is likely related to different reporting systems and thyroid cancer incidence. Cytologic features such as nuclear pleomorphism, nuclear crowding, microfollicular pattern, and dyshesive cell pattern were found to be useful in diagnosing FTCs more effectively.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

Objective:To identify the influencing factors of maternal anxiety, and explore the moderating role of co-parenting in the effect of marriage quality on maternal anxiety.Methods:Totally 522 mothers with children aged 0-12 were enrolled in the surveys and completed the Generalized Anxiety Disorder (GAD-7), Marital Adjustment Test and Co-parenting Relationship Scale.The chi-square test, the spearman correlation analysis and non-parametric percentile Bootstrap method were processed by SPSS 22.0.Results:①The detection rate of anxiety in the mothers was 48.7%, and the rate for mild, moderate, and severe anxiety was 37.4%, 8.4%, 2.9%, respectively.② The chi-square test showed that the family factors, such as mother's age, level of workload, family economic conditions, husband's level of workload, the child's age and health condition, as well as the conflicts between parents and grandparents and the grandparents’ willingness of involving in raising children, significantly affected mother’s anxiety(χ 2=4.292-23.170, P<0.05). ②The maternal anxiety was negatively correlated with marital quality ( r=-0.419, P<0.01). ③ Both positive co-parenting (PCP) and negative co-parenting(NCP) played moderating roles in the relationship between marriage quality and maternal anxiety( BPCP=0.013, P<0.01; BNCP=-0.010, P<0.05). Conclusion:Marital quality is an important factor which affects maternal anxiety, and father’s performance in co-parenting plays a moderating role in it.

Objective:To evaluate the interobserver variation of pathologists in the morphological evaluation of non-invasive follicular thyroid neoplasm with papillary-like nuclear features(NIFTP).Methods:Nine pathologists from different regions in China were selected to evaluate the digital slides of 30 cases of NIFTP. Three score system was applied, including nuclear size and shape, membrane irregularity, and chromatin features. Individual histologic features were scored as either present(1)or absent(0). A total score of 0 or 1 was considered inadequate for the diagnosis of NIFTP and a total score of 2 or 3 was considered sufficient for the diagnosis of NIFTP.Results:Overall, 9 doctors had weak consistency in the interpretation of the 30 cases(Kappa value 0.081 4), in which the interpretation of the membrane irregularity had the best consistency(Kappa value 0.193 6)and the interpretation of nuclear size and shape revealed the worst consistency(Kappa value 0.102 2). The overall consistency of the evaluation from the 7 senior pathologists was better than that of all the pathologists(Kappa value 0.134 1), but it was still weak. The consistency of nuclear membrane irregularity(Kappa value 0.267 4)and nuclear chromatin features(Kappa value 0.257 3)was weak, but much better than that of nuclear size and shape(Kappa value 0.073 0). The interobserver consistency in our study was lower than that in Asian study generally. However, the judgement on membrane irregularity in our senior pathologists was better than that in Asian study.Conclusion:The interobserver variation on the evaluation of the nuclear features of NIFTP is probably due to the education level, working experience, personal understanding of the diagnostic criteria, the regional difference, and some uncertain reasons. There is overall a weak consistency in the interpretation of NIFTP by Chinese pathologists, and it is necessary to popularize the diagnostic criteria and specify the criteria in detail. It is important to exclude high-risk genetic mutation using immunohistochemical staining or molecular examination on those patients with morphology of NIFTP.