Paediatric hepatic angiosarcoma with consumptive hypothyroidism-an important diagnostic pitfall to avoid during evaluation of hepatic vascular tumours.

Hepatic angiosarcoma is an extremely rare primary malignant vascular tumour in children with very poor prognosis. Radiological diagnosis of hepatic angiosarcoma is challenging due to overlapping imaging features with other benign vascular hepatic tumours, particularly infantile hepatic haemangioma. Consumptive hypothyroidism is a condition that is almost exclusively associated with infantile hepatic haemangioma and has never been reported in angiosarcoma. We present a case of hepatic angiosarcoma in a 20-month-old girl, associated with consumptive hypothyroidism and, as a result, initially misdiagnosed as infantile hepatic haemangioma. Radiologists should be aware that consumptive hypothyroidism is not a reliable feature to use in excluding paediatric hepatic angiosarcoma. Biopsy should be performed in patients older than 1 year of age or with atypical imaging features.

DICER1 -Altered Extraovarian Moderately Differentiated Sertoli-Leydig Cell Tumor: Report of a Rare Case.

We report an unusual case of a pelvic extraovarian moderately differentiated Sertoli-Leydig cell tumor arising in a 4-yr-old female. The tumor contained a DICER1 pathogenic variant which was absent in the germline ruling out DICER1 syndrome. In reporting this case, we discuss the differential diagnosis and possible histogenesis and review reported cases of extraovarian Sertoli-Leydig cell tumor.

Epidemiology and outcomes of pediatric transplant-associated thrombotic microangiopathy in Hong Kong.

BACKGROUND: Transplant-associated thrombotic microangiopathy (TA-TMA) is an under-recognized yet potentially devastating complication of hematopoietic stem cell transplantation (HSCT) which had increased awareness in recent years. This report summarizes the demographics and outcomes of pediatric TA-TMA in Hong Kong. METHODS: All patients aged below 18 years who underwent HSCT in the Hong Kong Children's Hospital and were diagnosed to have TA-TMA during the 2-year period from April 1, 2019 to March 31, 2021 were included. RESULTS: A total of 73 transplants (51 allogeneic and 22 autologous) in 63 patients had been performed. Six patients (four males and two females) developed TA-TMA at a median duration of 2.5 months post-HSCT. The incidence rate was 9.52%. Of the six TA-TMA patients, five underwent allogenic one underwent autologous HSCT, respectively. Three of them were histologically proven. All four patients with cyclosporine had stopped the drug once TA-TMA was suspected. Median six doses of eculizumab were administered to five out of six patients. Three patients died (two due to fungal infection and one due to acute-on-chronic renal failure) within 3 months upon diagnosis of TA-TMA. Among three survivors, two stabilized with mild stage 2 chronic kidney disease (CKD) while the other suffered from stage 5 end-stage CKD requiring lifelong dialysis. CONCLUSION: In conclusion, recognition and diagnosis of TA-TMA are challenging. Early recognition and prompt administration of complement blockage with eculizumab may be beneficial in selected cases. Further prospective research studies are recommended to improve the management and outcomes of TA-TMA.

Novel finding of lissencephaly and severe osteopenia in a Chinese patient with SATB2-associated syndrome and a brief review of literature.

SATB2-associated syndrome (SAS) is a rare disorder characterized by developmental delay, behavioral problems, and craniofacial anomalies in particular dental and palatal abnormalities. We describe the clinical course, genetic and autopsy findings in a Chinese boy with global developmental delay, hypotonia, epilepsy, recurrent fractures and osteopenia. Brain magnetic resonance imaging showed pachygyria, white matter hypoplasia and hypogenesis of the corpus callosum. Whole-exome sequencing identified a novel heterozygous missense variant c.1555G>A p.(Glu519Lys) in the SATB2 gene. Unfortunately, he died at 26 months of bronchiolitis and pneumonia. Autopsy revealed pachygyria which was more severe anteriorly, dilated lateral and third ventricles and partial agenesis of the corpus callosum. Histology showed features compatible with two-layered lissencephaly. The bone showed disordered lamination and bone matrix. Although SATB2 has been shown to be involved in the regulation of neuronal migration in the developing brain, lissencephaly has not been reported so far. This could represent a more severe phenotype of SAS.

A Fetus with Congenital Microcephaly, Microphthalmia and Cataract Was Detected with Biallelic Variants in the OCLN Gene: A Case Report.

Microcephaly and microphthalmia are both rare congenital abnormalities, while concurrently, these two are even rarer. The underlying etiology would be complex interplaying between heterogeneous genetic background and the environmental pathogens, particularly during critical periods of early tissue development. Here, we reported a prenatal case with microcephaly, microphthalmia, and bilateral cataracts detected by ultrasonography and confirmed by autopsy. Various routine infection-related tests and invasive genetic testing were negative. Whole genome sequencing of fetus and parents revealed OCLN gene defects may be associated with these multiple congenital abnormalities.

A 7-year-old boy dying of acute encephalopathy.

A 7 year old Chinese boy died of a rapidly progressive encephalopathy after influenza infection. MRI showed bilateral and symmetrical lesions including the thalamus and brainstem tegmentum. The pathology of necrosis and vasculopathy were in keeping with acute necrotizing encephalopathy (ANE). ANE was first described in Japan and carries a high mortality and morbidity. A vasculopathy with breakdown of the blood-brain-barrier was incriminated but the pathogenesis remained obscure and autopsy studies have been limited. A review of the literature showed only nine postmortem reports in the acute stage. Symmetrical brain necrosis always involved the thalamus followed by the tegmentum of the pons and other regions. Exudative vasculopathy was commonly observed and often accompanied by endothelial cell necrosis. In the present case there was inflammatory fibrinoid vasculitis which has not been previously described.

Systemic infection of avian influenza A virus H5N1 subtype in humans.

The viral dissemination in a patient with avian influenza A subtype H5N1 infection was retrospectively studied by the immunohistochemical localization of viral nucleoprotein antigen. The pathology was marked by diffuse alveolar damage, lymphoid depletion, and reactive hemophagocytic syndrome. Besides the lung and the upper respiratory tract, viral antigen was detected in the small and large intestinal epithelial cells, hematopoietic cells in the bone marrow, glial cells and neurons of the brain, and lymphocytes. The results confirmed that H5N1 virus disseminated to multiple organs beyond the respiratory system. However, specific pathological changes were noted in the respiratory system only, and productive viral replication confirmed by culture was noted only in the lung. More postmortem studies are needed to elucidate the pathogenesis of this highly fatal zoonotic disease.

Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer.

Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy.

The comparative pathology of severe acute respiratory syndrome and avian influenza A subtype H5N1--a review.

The pathology of 2 zoonotic human viral infections that recently emerged, severe acute respiratory syndrome (SARS) due to coronavirus (SARS-CoV) and avian influenza A subtype H5N1, is reviewed and compared based on the literature and the cases examined by the authors. Pneumocytes are the primary target of infection resulting in diffuse alveolar damage. Systemic cytokine activation results in hemophagocytic syndrome, lymphoid depletion, and skeletal muscle fiber necrosis. Severe acute respiratory syndrome induces a more fibrocellular intra-alveolar organization with a "bronchiolitis obliterans organizing pneumonia"-like pattern and presence of multinucleated histiocytes and pneumocytes. H5N1 causes a more fulminant and necrotizing diffuse alveolar damage with patchy and interstitial paucicellular fibrosis. Severe acute respiratory syndrome associated coronavirus persists in the lung up to the second month, whereas H5N1 persists in the lung up to the third week. Severe acute respiratory syndrome associated coronavirus disseminates to blood, urine, feces, gastrointestinal tract, and liver. There is recent report of possible cerebral involvement by H5N1 and its isolation in the blood, gastrointestinal tract, and cerebrospinal fluid. More pathologic studies are urgently needed.

Intraoperative frozen section for detecting active infection in failed hip and knee arthroplasties.

The authors reported the result of 40 sessions of intraoperative frozen section on polymorph count in 33 patients undergoing exploration or revision hip and knee surgery to detect active infection. The correlation rate between frozen section and permanent section was 0.95 to 1.00. If the polymorph count more than 5 per high-power field (40 X) was chosen as positive, the sensitivity, specificity, positive predictive value, and negative predictive value would be 0.93, 0.77, 0.68, and 0.95, respectively. Taking polymorph count of more than 10 as positive, the sensitivity, specificity, positive predictive value, and negative predictive value would then be 0.86, 0.85, 0.75, and 0.92, respectively. The authors concluded that intraoperative frozen section is an inexpensive, rapid, and helpful adjunct to detect active infection. A polymorph count of lower than 5 highly suggests the absence of active infection.

Myopathic changes associated with severe acute respiratory syndrome: a postmortem case series.

BACKGROUND: The March 2003 outbreak of the severe acute respiratory syndrome (SARS) resulted in significant morbidity and mortality. Muscle weakness and elevated serum creatine kinase levels are commonly encountered in patients with SARS. However, the nature and cause of myopathy associated with a SARS infection are unknown because, to our knowledge, there has been no report of histological or postmortem examination of the skeletal muscle from SARS-infected patients. OBJECTIVE: To determine the exact nature of the myopathy associated with SARS. METHOD: Postmortem skeletal muscles from 8 consecutive patients who died of SARS in March 2003 were studied under light and electron microscopy as well as immunohistochemistry. RESULTS: Focal myofiber necrosis was identified in 4 of 8 cases. Macrophage infiltration and regenerative fiber were scanty. All 4 patients treated with a steroid had significant myofiber atrophy. In situ hybridization for coronavirus was negative in all subjects. Viral cultures for coronavirus and examination for viral particles under electron microscopy were performed in 2 patients. The viral culture yielded no organisms and there were no viral particles seen on electron microscopic examination. CONCLUSIONS: There is a spectrum of myopathic changes associated with a SARS infection. Focal myofiber necrosis is common and possibly is immune mediated. Critical illness myopathy and superimposed steroid myopathy may also play an important role in SARS.

Direct sequencing of SARS-coronavirus S and N genes from clinical specimens shows limited variation.

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged, in November 2002, as a novel agent causing severe respiratory illness. To study sequence variation in the SARS-CoV genome, we determined the nucleic acid sequence of the S and N genes directly from clinical specimens from 10 patients--1 specimen with no matched SARS-CoV isolate, from 2 patients; multiple specimens from 3 patients; and matched clinical-specimen/cell-culture-isolate pairs from 6 patients. We identified 3 nucleotide substitutions that were most likely due to natural variation and 2 substitutions that arose after cell-culture passage of the virus. These data demonstrate the overall stability of the S and N genes of SARS-CoV over 3 months during which a minimum of 4 generations for transmission events occurred. These findings are a part of the expanding investigation of the evolution of how this virus adapts to a new host.

Outcomes and prognostic factors in 267 patients with severe acute respiratory syndrome in Hong Kong.

BACKGROUND: Severe acute respiratory syndrome (SARS) has become a global public health emergency. OBJECTIVE: To evaluate the characteristics and outcomes of patients with SARS in Hong Kong and to identify predictors of mortality. DESIGN: Retrospective cohort study. SETTING: Quarantine hospital for patients with SARS in Hong Kong. PATIENTS: 267 consecutive patients hospitalized from 26 February to 31 March 2003 for probable or confirmed SARS. MEASUREMENTS: Clinical, laboratory, and radiographic measures; 3-month mortality rate. RESULTS: According to our case definition, there were 227 cases of confirmed SARS and 40 cases of probable SARS. Common presenting symptoms were fever (99% of patients), chills (74%), malaise (63%), and myalgia (50%). Laboratory findings included lymphopenia (73%), thrombocytopenia (50%), hyponatremia (60%), and elevated levels of lactate dehydrogenase (47%) and C-reactive protein (75%). During hospitalization, incidence of diarrhea (53%), anemia (53%), and acute renal failure (6%) increased. Sixty-nine patients (26%) required intensive care because of respiratory failure. The 3-month mortality rate was 12% (95% CI, 8% to 16%). Factors contributing to mortality were respiratory failure, acute renal failure, and nosocomial sepsis. On multivariate Cox regression, age older than 60 years (relative risk, 5.10 [CI, 2.30 to 11.31]; P < 0.001) and lactate dehydrogenase level greater than 3.8 micro kat/L at presentation (relative risk, 2.20 [CI, 1.03 to 4.71]; P = 0.04) were independent predictors of mortality. CONCLUSION: Because of the longer follow-up period in our cohort, the mortality rate in these patients is higher than rates reported in previous studies. Advanced age and high lactate dehydrogenase level at presentation predict mortality. *For members of the Princess Margaret Hospital SARS Study Group, see the Appendix.

Anatomy of the portal vein bifurcation: implication for transjugular intrahepatic portal systemic shunts.

PURPOSE: The relationship of the portal vein bifurcation to the liver capsule in Asians, which is an important landmark for transjugular intrahepatic portosystemic shunt, has not previously been described. METHODS: The anatomy of the portal vein bifurcation was studied in 70 adult Chinese cadavers; it was characterized as intrahepatic or extrahepatic. The length of the exposed portion of the right and left portal veins was measured when the bifurcation was extrahepatic. RESULTS: The portal vein bifurcation was intrahepatic in 37 cadavers (53%) and extrahepatic in 33 cadavers (47%). The mean length of the right and left extrahepatic portal veins was 0.96 cm and 0.85 cm respectively. Both were less than or equal to 2 cm in 94% of the cadavers with extrahepatic bifurcation. There was no correlation between the presence of cirrhosis and the location of the portal vein bifurcation (p = 1.0). There was no statistically significant difference in liver mass in cadavers with either extrahepatic or intrahepatic bifurcation (p = 0.40). CONCLUSIONS: These findings suggest that for transjugular intrahepatic portosystemic shunt placement, a portal vein puncture 2 cm from the bifurcation will be safe in most cases.