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.

Oncocytic variant of medullary thyroid carcinoma: 3 cases report with review of literatures / 临床与实验病理学杂志

Purpose To investigate the clinicopathologic features and differential diagnosis of oncocytic variant of medullary thyroid carcinoma (MTC).Methods Morphological,immunohistochemical findings on 3 oncocytic variant of MTC cases and electron microscopic findings on 2 of these 3 cases were studied,with review of the relevant literatures.Results The cytoplasm was abundant,eosinophilic and granular with defined margins.The nuclei were enlarged,round to oval.Prominent nucleoli were identified in some cells.Tumor cells formed sheets,trabeculae or follicles with infiltrative pattern.Immunohistochemically,thyroglobulin (TG) was negative in all 3 cases.Calcitonin was positive in 2 cases and negative in 1 case.Ultrastructurally,a large number of mitochondria and various neuroendocrine granules were found in the 2nd and 3rd cases.Conclusion Oncocytic variant of MTC is very rare with variable histopathologic appearances.It should be considered in diagnosing oncocytic lesions of thyroid.A definite diagnosis can be rendered based on comprehensive findings of the immunohistochemistry,serology study and electron microscopy.It needs to avoid misdiagnosis and missed diagnosis.