Clinicopathological features of hepatic fibrinogen storage disease in children / 中华病理学杂志

Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.

Postoperative clinicopathological features of the patients with micropapillary lung adenocarcinoma / 医学研究生学报

Objective　Studies are rarely reported on the factors influencing prognosis of surgically resected lung adenocarcinoma with a micropapillary pattern (LAC-MPP). This study aimed to explore the clinicopathological characteristics and risk factors of surgically resected LAC-MPP. Methods　We retrospectively analyzed 384 cases of LAC treated in Henan Cancer Hospital between June 2015 and December 2017, which were classified into an MPP group (n = 82) and a non-MPP control group (n = 302) according to the results of postoperative pathology. We determined the expression of the fusion protein anaplastic lymphoma kinase (ALK), analyzed its association with the clinicopathological features of LAC-MPP, and explored the risk factors of postoperative MPP. Results　Compared with the non-MPP group, the LAC-MPP patients showed a significantly higher expression of ALK (0.03% vs 12.20%, P < 0.05), rate of bronchial invasion (30.80% vs 48.78%, P < 0.05) and vascular tumor thrombus (0.99% vs 25.61%, P < 0.05), but a lower mutation rate of the epidermal growth factor receptor (EGFR) (64.24% vs 51.22%, P < 0.05). Multivariate logistic regression analysis revealed that the expression of ALK, vascular tumor thrombus, and age were significantly associated with the risk of postoperative MPP. Conclusion　There is a high incidence rate of ALK expression in LAC-MPP patients after operation, which may provide some new ideas for the clinical treatment of the disease. Special attention should be paid to the expression of the ALK fusion protein and vascular tumor thrombus, and age in patients with LAC-MPP after operation.