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Primary spinal cord astrocytoma (SCA) is a rare disease. Knowledge about the molecular profiles of SCAs mostly comes from intracranial glioma; the pattern of genetic alterations of SCAs is not well understood. Herein, we describe genome‐sequencing analyses of primary SCAs, aiming to characterize the mutational landscape of primary SCAs. We utilized whole exome sequencing (WES) to analyze somatic nucleotide variants (SNVs) and copy number variants (CNVs) among 51 primary SCAs. Driver genes were searched using four algorithms. GISTIC2 was used to detect significant CNVs. Additionally, recurrently mutated pathways were also summarized. A total of 12 driver genes were identified. Of those, H3F3A (47.1%), TP53 (29.4%), NF1 (19.6%), ATRX (17.6%), and PPM1D (17.6%) were the most frequently mutated genes. Furthermore, three novel driver genes seldom reported in glioma were identified: HNRNPC, SYNE1, and RBM10. Several germline mutations, including three variants (SLC16A8 rs2235573, LMF1 rs3751667, FAM20C rs774848096) that were associated with risk of brain glioma, were frequently observed in SCAs. Moreover, 12q14.1 (13.7%) encompassing the oncogene CDK4 was recurrently amplified and negatively affected patient prognosis. Besides frequently mutated RTK/RAS pathway and PI3K pathway, the cell cycle pathway controlling the phosphorylation of retinoblastoma protein (RB) was mutated in 39.2% of patients. Overall, a considerable degree of the somatic mutation landscape is shared between SCAs and brainstem glioma. Our work provides a key insight into the molecular profiling of primary SCAs, which might represent candidate drug targets and complement the molecular atlas of glioma. © 2023 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinicopathological features, immunophenotype, molecular genetics and prognosis of extraskeletal mesenchymal chondrosarcoma in central nerve system (CNS). Methods: The clinicopathological findings, immunohistochemistry and genetic analysis of four cases of extraskeletal mesenchymal chondrosarcoma in Xuanwu Hospital between 2014 and 2019 were reviewed and followed up. Results: The ages of patients ranged from 20-35 years. Three patients had intracranial lesions and one had intradural tumor. The characteristic histologic features were undifferentiated small cells together with scattered islands of hyaline cartilage. There was hemangiopericytoma-like pattern with calcification and ossification. The tumor cells were positive for VIM and SOX9; and the small cells were positive for CD99, NSE and NKX3.1. The cells in chondroid matrix were positive for S-100. All tumor cells were negative for markers including CKpan, EMA and desmin. At molecular analysis, HEY1-NCOA2 fusion transcripts were identified in three patients. The fusion points were between exon 4 of HEY1 and exon 13 of NCOA2 . Follow-up information was obtained in two patients, and both were free from recurrence or metastasis at 8 and 20 months. Conclusions: Extraskeletal mesenchymaI chondrosarcoma is a rare CNS disease with poor prognosis. In addition to SOX9, NKX3.1 can be another useful antibody for the differential diagnosis. The combination of pathological characteristics, immunophenotype and genetic profile of tumor is essential for diagnosis.

Encapsulated papillary carcinoma (EPC) of the breast is typically of low-to-intermediate grade (LTIG) with favorable prognosis. Rarely, high-grade (HG) EPC cases have been documented in recent years. Herein we compared the morphological, immunohistochemical, and clinical features of LTIG EPC to those of HG EPC. Of the 30 EPC patients, 25 were diagnosed as LTIG and five as HG (median age: 60 and 36 years, respectively); 80% of the HG EPCs exhibited predominantly solid architecture with prominent lymphoplasmacytic infiltrates, more crowded and thicker papillae, and greater stratification and irregular arrangement of malignant epithelial cells. Coexisting invasive components were observed in 32% and 80% of LTIG and HG cases, respectively. HG EPC was negative for hormone receptor staining. Additionally, 48% of LTIG EPC cases were moderately positive for human epidermal growth factor receptor 2 (Her-2) immunostaining (2+); among them, one case showed Her-2 gene amplification by fluorescence in situ hybridization. The basal-like markers cytokeratin 5/6 and epidermal growth factor receptor were detected in two and five HG cases, respectively. HG EPC was also characterized by a significantly high Ki-67 index (median: 85%, P<0.001). No local recurrence or distant metastasis was noted during the follow-up. HG EPC typically exhibited a solid architecture with a concurrent invasive component as well as a triple-negative and basal-like immunophenotype in young women. HG EPC might be indicative of high proliferative activity and potential aggressiveness.

MGMT promoter methylation is considered as a prognostic and predictive biomarker indicating response to chemotherapy and radiotherapy in glioblastoma. A number of different methods and platforms including pyrosequencing (PSQ), quantitative methylation-specific PCR (qMSP) and immunohistochemistry (IHC), methylation-sensitive high resolution melting (MS-HRM) and NGS (Next Generation Sequencing) have been used to detect MGMT promoter methylation in gliomas. However, controversy remains about the most appropriate method to use for analyzing MGMT status. The MGMT promoter methylation status of a total of 350 gliomas and gangliogliomas was examined using PSQ, qMSP and IHC in parallel. Using PSQ as a recommended standard method, the sensitivity, specificity, positive/negative predictive value and correlation with the other assays were calculated. Among 350 glioma and ganglioglioma cases, the MGMT promoter tested positive for methylation in 53.1%, 55.4%, and 70.3% of the cases by PSQ, qMSP and IHC, respectively. The sensitivity and specificity of qMSP were 97.8% and 92.7%, respectively. Twelve cases that tested positive for methylation using qMSP were negative according to PSQ, and four cases that were negative according to qMSP tested positive according to PSQ. The concordance rate between PSQ and qMSP was 90.8%. The sensitivity and specificity of IHC for the detection of MGMT at the protein level were 84.4% and 45.7%, respectively. The concordance rate between PSQ and IHC was 30.8%. This study demonstrated that qMSP is an effective and rapid detection method for routine use in pathology laboratories for the identification of MGMT promoter methylation. A combination of IHC and qMSP assays can provide high sensitivity and specificity for the prediction of MGMT status. A few cases that tested negative with PSQ did harbor MGMT promoter methylation, as confirmed by qMSP and sequencing, and this subgroup of patients may benefit from temozolomide., (Copyright © 2017. Published by Elsevier GmbH.)

Thymic adenocarcinoma of the mediastinum is extremely rare. Only 12 cases adenocarcinoma associated with a thymic cyst have been reported in the literature. In this report, we describe a case of a thymic adenocarcinoma associated with thymic cyst. A 70-year-old man, presented with two months of chest tightness, breath shortness and chest pain. The contrast enhanced CT scan of chest revealed a round, cystic mass in right anterior mediastinum. Microscopic examination revealed that the lining consisted of flat to cuboidal and columnar epithelium and adenocarcinoma infiltrated into the thymic tissue and the soft tissue around the wall of cyst. Based on clinical history, imaging studies, pathological findings and absence of extramediastinal tumor, a diagnosis of thymic adenocarcinoma associated with thymic cyst was established. The patient was alive without any sign of recurrence 7 months after the operation.

Background: BRAF V600E is the most frequent genetic alteration in papillary thyroid carcinoma (PTC); there are ongoing conflicts on its association with regional lymph node metastasis. And we aimed to test this association in a referred sample in a single institute in China., Methods: We analyzed BRAF V600E mutational status in the primary lesion of 150 PTC cases in Peking Union Medical College Hospital (PUMCH) and their corresponding lymph node metastasis (if present and available) using a validated Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) method., Results: Among 150 PTC cases, 121 (80.6%) primary tumors harbored BRAF V600E mutation, 66.9% (81/121) and 79.3% (23/29) had regional lymph node metastasis (LNM) in cases detected with and without BRAF V600E mutation, respectively (P = 0.195). The BRAF V600E mutational status of most of the metastatic lesions was not different to that of their primary foci (73 out of 76 cases, 96.1%, Kappa value = 0.893). The 3 inconsistent cases were all mutation positive for primary tumors and mutation negative for LNM., Conclusion: No association was established between BRAF V600E mutation and regional lymph node metastasis in PTC in Chinese patients.

Objective: To study the expression and prognostic significance of ERG and SPINK1 expression in endocrine-treated prostatic cancer., Methods: Prostatic needle biopsies from 118 prostatic cancer patients primarily treated with endocrine therapy were reviewed. Immunohistochemical study for ERG and SPINK1 protein was carried out., Results: Co-expression of ERG and SPINK1 was not observed. The frequency of ERG protein expression in the 118 biopsies studied was 9.3% (11/118). The positive expression correlated with T stage (P=0.04) but not with patient age at diagnosis, prostatic specific antigen level, Gleason's score, M stage, tumor area and progression-free survival. Positive expression of SPINK1 was demonstrated in 11.0% (13/118) of the biopsies. SPINK1-positive cases carried a significantly shorter progression-free survival, as compared with SPINK1-negative cases (P=0.022). The expression was not associated with any other clinicopathologic variables. The following expression pattern showed statistically significant correlation with the clinical progress (P=0.029): ERG+/SPINK1- (11/118, 9.3%), ERG-/SPINK1+ (13/118, 11.0%) and ERG-/SPINK1- (94/118, 79.7%)., Conclusions: ERG and SPINK1 proteins are mutually exclusive.SPINK1 expression is associated with more aggressive clinical behavior and can serve as a prognostic biomarker in prostatic cancer.

The actin cross-linking protein filamin A (FLNa) functions as a scaffolding protein and couples cell cytoskeleton to extracellular matrix and integrin receptor signaling. In this study, we report that FLNa suppresses invasion of breast cancer cells and regulates focal adhesion (FA) turnover. Two large progression tissue microarrays from breast cancer patients revealed a significant decrease of FLNa levels in tissues from invasive breast cancer compared with benign disease and in lymph node-positive compared with lymph node-negative breast cancer. In breast cancer cells and orthotopic mouse breast cancer models, down-regulation of FLNa stimulated cancer cell migration, invasion, and metastasis formation. Time-lapse microscopy and biochemical assays after FLNa silencing and rescue with wild-type or mutant protein resistant to calpain cleavage revealed that FLNa regulates FA disassembly at the leading edge of motile cells. Moreover, FLNa down-regulation enhanced calpain activity through the mitogen-activated protein kinase-extracellular signal-regulated kinase cascade and stimulated the cleavage of FA proteins. These results document a regulation of FA dynamics by FLNa in breast cancer cells.

Objective: Although rare, invasive rhino-orbital-skull base aspergillosis usually is fatal and necessitates prompt diagnosis, surgical intervention and antifungal treatment., Method: A case series of 5 patients, with review of treatments and outcomes., Result: Five patients initially presented with orbital apex syndrome without apparent rhino-sinus disease. Histologic examination revealed invasive aspergillosis. Four patients underwent transnasal endoscopic surgical exploration of rhino-orbital-skull base, and three of them simultaneously underwent optic nerve decompression. One patient underwent the rhinopharyngeal biopsy. Following surgical debridement and antifungal drug, Two patients achieved various degree of recovery, 1 patient (case 5) showed vision improvement, from counting fingers to 0.1 and symptom-free during 65 months follow-up. One patient (case 1) showed no recovery of vision from no light perception, but symptom-free during 43 months follow-up. Other three patients respectively died of massive intracranial spread (case 3), postoperative brainstem hemorrhage (case 2) and sepsis (case 4)., Conclusion: Invasive sino-orbital-skull base aspergillosis often may resemble inflammatory conditions. Early diagnosis and surgical intervention are required to improve vision and survival. The endoscopic surgical exploration and biopsy often are necessary to rule out fungal sinus infection before considering steroid use, especially in immunocompromised individuals. The patients with invasive rhino-orbital-skull base aspergillosis usually have a poor prognosis.