Diagnostic utility of genetic alterations in distinguishing IDH-wildtype glioblastoma from lower-grade gliomas: Insight from next-generation sequencing analysis of 479 cases.

The accurate diagnosis and classification of gliomas are essential for appropriate treatment planning and prognosis prediction. This study aimed to investigate the molecular diagnostics of IDH-wildtype diffuse astrocytic gliomas and identify potential genetic variants that could differentiate glioblastoma (GBM) from lower-grade gliomas when DNA methylation analysis is not feasible. In total, 479 H3-and IDH-wildtype diffuse astrocytic gliomas were included in this study. All the cases were diagnosed according to the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors. Panel sequencing data were collected, and clinicopathological information was retrieved from medical records. Genetic alterations and histological findings were analyzed to determine their diagnostic utility and prognostic implications. Out of 479 cases, 439 (91.6%) were diagnosed with GBM, including 28 cases that were molecularly diagnosed as GBM. However, 40 (8.4%) cases could not be classified according to the 2021 WHO classification and were diagnosed as lower-grade diffuse astrocytic glioma, IDH-wildtype, not elsewhere classified (LGNEC). In addition to the three genetic alterations included in the diagnostic criteria of GBM, PTEN and EGFR mutations were found to be enriched in GBM. Patients harboring mTOR pathway mutations demonstrated a more favorable prognosis and often exhibited morphology resembling subependymal giant cell astrocytoma, along with a high tumor mutational burden. Among patients with mTOR pathway mutations, those lacking molecular diagnostic features of GBM exhibited outstanding survival outcomes, even in the presence of grade 4 histology. Integration of molecular features enhanced the diagnostic accuracy of IDH-wildtype gliomas. Some molecular alterations enriched in GBM offer valuable insights for molecular diagnosis and glioma classification. Furthermore, high-grade diffuse astrocytic gliomas featuring mTOR pathway mutations in the absence of molecular diagnostic features of GBM could represent more favorable tumor types distinct from GBM.

Colon cancer microsatellite instability influences computed tomography assessment of regional lymph node morphology and diagnostic performance.

PURPOSE: To elucidate whether a high level of microsatellite instability (MSI-high) in colon cancer influences the CT assessment of regional lymph node (rLN) morphology and diagnostic performance on predicting pathological node-negative (pN0) patients. METHOD: We retrospectively reviewed 507 patients with cecal/proximal ascending colon cancer (age, 63.0 ± 11.6 years; MSI-stable, n = 398; MSI-high, n = 109) who underwent right hemicolectomy between July 1, 2009, and December 31, 2018. Preoperative CT images were assessed for number of rLNs, long/short diameter of the largest rLN, and CT LN grade (CTN0, low probability of metastasis; CTN1, borderline; CTN2, high probability). Sensitivity, specificity, positive predictive value and negative predictive value for predicting pN0 was calculated. Multivariable logistic regression analysis was performed. Statistical significance was defined as P < 0.05. RESULTS: A study population of 507 patients (mean age ± standard deviation, 63.0 ± 11.6; 264 women) were evaluated. In patients with rLN metastasis, the rLN long axis (pN1: P = 0.013, pN2: P = 0.039) and short axis (pN1: P = 0.001, pN2: P = 0.009) were both longer in MSI-high tumors compared with MSI-stable tumors. High specificity for predicting pN0 was only achieved in MSI-high tumors [sensitivityMSI-stable = 58.3% (n = 137/235), specificityMSI-stable = 71.2% (n = 116/163); sensitivityMSI-high = 38.4% (n = 33/86), specificityMSI-high = 91.3% (n = 21/23)]. Multivariable logistic regression indicated MSI-high (P < 0.001, odds ratio = 3.701), smaller LN long axis (P = 0.023, odds ratio = 0.905), and lower CT LN grade (CTN0: P = 0.009, odds ratio = 2.987; CTN1: P = 0.014, odds ratio = 2.195) as significant parameters in predicting pN0. CONCLUSION: MSI-high colon cancer is associated with larger rLNs and high specificity for predicting pN0 on CT assessment.

Metastatic leiomyosarcoma of the thyroid gland: cytologic findings and differential diagnosis.

Metastatic leiomyosarcoma to the thyroid is an extremely rare occurrence, and only 18 cases have been reported. Here, we report a case of a 37-year-old woman who presented with multiple masses on the scalp. Excisional biopsy was done and the mass revealed fascicles of smooth muscle fibers which showed positive staining for smooth muscle actin, thus confirming the diagnosis of leiomyosarcoma. The patient was also found to have a 0.9 cm mass within the left thyroid. Fine-needle aspiration was done and the cytological smear showed hypercellular spindle cell clusters with hyperchromatic and large nuclei. Normal thyroid follicular cells were found within or around tumor cells. In this report, we present the cytologic findings of metastatic leiomyosarcoma to the thyroid and offer differential diagnoses of the aspirated spindle cells.

Mesonephric-like Differentiation of Ovarian Endometrioid and High-grade Serous Carcinomas: Clinicopathological and Molecular Characteristics Distinct from Those of Mesonephric-like Adenocarcinoma.

BACKGROUND/AIM: Ovarian endometrioid carcinoma (EC) and high-grade serous carcinoma (HGSC) may exhibit various growth patterns and mimic mesonephric-like adenocarcinoma (MLA). We investigated the clinicopathological and molecular features of ovarian carcinomas with mesonephric-like differentiation (MLD). PATIENTS AND METHODS: We analyzed the electronic medical records and pathology slides of two EC-MLD and three HGSC-MLD patients, and conducted immunostaining and targeted sequencing of their samples. RESULTS: All cases showed architectural diversity, compactly aggregated small tubules and ducts, and eosinophilic intraluminal secretions, indicating the possibility of an ovarian MLA. However, the following histological and immunophenotypical features confirmed the diagnoses of EC-MLD and HGSC-MLD: squamous, tubal, and sertoliform differentiation; serous tubal intraepithelial carcinoma; solid, endometrioid, transitional (SET) feature; solid, transitional, endometrioid, mucinous-like (STEM) feature; diffuse expression of hormone receptors and Wilms tumor 1; mutant p53 immunostaining pattern; and wild-type v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog gene. CONCLUSION: A subset of ovarian ECs and HGSCs can display MLD and mimic an MLA. A thorough histological examination combined with ancillary tests is crucial to differentiate between these ovarian neoplastic entities.

Superficially Spreading Endocervical Adenocarcinoma in situ with Multifocal Microscopic Involvement of the Endometrial Surface: A Case Report with Emphasis on the Potential for Misdiagnosis Based on Endometrial Curettage Specimens.

Misdiagnosis of endocervical adenocarcinoma (EAC) as endometrial endometrioid carcinoma (EEC) is one of the major concerns when evaluating endometrial curettage specimens. It is difficult to differentiate EAC involving the endometrium from EEC, particularly when the specimens have only a few small tumor fragments. We report a case of endocervical adenocarcinoma in situ (AIS) with multifocal microscopic involvement of the endometrium. The endometrial curettage specimen obtained from an 82-year-old woman consisted of a large volume of blood and fibrin, with small endometrial tissue fragments showing microscopic foci of atypical glandular proliferation. Based on the presence of complex glands with stratified mucin-poor columnar epithelium and intermediate-grade nuclear atypia, a preoperative diagnosis of grade 1 EEC was made. However, the hysterectomy specimen revealed an endocervical AIS involving the endocervix and low uterine segment. Frequent mitotic figures and apoptotic bodies, characteristic of AIS, were present. The endometrium showed a few microscopic foci of atypical glandular proliferation involving the surface only. Their histological features were similar to those of the endocervical AIS. Immunohistochemically, the atypical glands exhibited block p16 positivity. The final diagnosis was a superficially spreading endocervical AIS with multifocal microscopic involvement of the endometrial surface epithelium. In summary, small tumor tissues in an endometrial curettage may lead to misdiagnosis of AIS or EAC as EEC, especially when the pathologists are unaware of the possibility of microscopic endometrial involvement of AIS or EAC. The origin of the tumor can be correctly determined based on a combination of histological features and immunostaining. Endocervical AIS involving the endometrium should be included in the differential diagnosis of neoplastic glandular lesions in endometrial curettage specimens. An accurate diagnosis in these cases is important because of its significant implications for clinical management.