MALIGNANT HISTIOCYTOSIS: A STUDY ON CLINICOPATHOLOGICAL FEATURES AND CELL ORIGIN

Thirty- one autopsy cases previously diagnosed as malignant histiocytosis (MH) were studied by means of immunohistochemical staining. Antibodies detecting the formalin resistant epitopes on T- cells, B- cells and those of histiocyte/monocyte origin were used. It was shown that the malignant histiocytes reacted only to the cell markers derived from histlocyte/monocyte. and only a part of lymphocytes showed positive reaction to the T and B cell markers. It is suggested that the histiocyte/monocyte lineage is the possible origin of the malignant proliferating cells in MH. The clinicopathological features and the differentiation of MH from familial erythrophagocytic lymphohistiocytosis, virus-associated hemophagocytic syndrome and malignant lymphoma are described. The pathogenesis. the causes of death and the points for attention in the treatment of MH are also discussed.

Ultrasonographic diagnosis of urinary calculus caused by melamine in children

Background Intake of melamine can cause renal and ureteral lithiasis in infants and children. The present study aimed to understand the value of ultrasonography in the diagnosis of renal and ureteral lithiasis in infants and young children caused by melamine, and the characteristics of ultrasonograms of melamine-associated calculi. Methods Ultrasonographic examination on the urinary system was performed for 28 332 children who ingested milk powder that was possibly tainted with melamine; 395 of the children were diagnosed by ultrasonography as having urinary calculus, and 231 cases had lump-like calculi and 164 cases had sand gravel-like calculi. The features of the calculi, the sites of obstruction and the status of hydronephrosis and hydroureterosis were analyzed. Ultrasonographic reexamination was performed for 116 patients and the findings were compared with those of the first ultrasonography, and the short-term expulsion of the calculi was evaluated. Results Most of the 395 patients with urinary lithiasis, except for those who developed renal failure, had no symptoms. The whole profile of the calculi could be seen in most of the cases, because the echogenicity of the calculi with no sharp or absent acoustical shadowing, was weaker as compared with those from calcium-containing calculi. Comet tail sign could be seen behind the echogenicity of single gravel calculus. The rate of diagnostic consistency of ureteral lithiasis between the ultrasound and the results of clinical observation （including stones expelled spontaneously or after cystoscopic intervention） in 51 cases for 76 ureters was 100%. Percutaneous renal biopsy was performed for one case, and histopathological examination showed flocculent, fine strip-like, ellipse and circular deeply stained sand gravel-like material in the renal tubules, and the circular calculi were found to be attached to the walls of the tubules. Chemical analysis of the calculi expelled from 12 cases showed that the main contents of the calculi were uric acid and melamine. Short-term ultrasound reexamination in 116 patients showed that gravel-like calculi disappeared in 80.4% of the cases; in 26 non-hospitalized cases who had lump-like calculi without hydronephrosis or hydroureterosis, none of the lump-like calculi were expelled. Conclusions The ultrasonograpic findings of urinary calculi in children caused by ingestion of melamine-tainted milk powder have a certain features as compared to the calculi containing calcium. Careful ultrasound examination can avoid missed diagnoses of ureteral calculi. Most of the gravel-like calculi can be expelled within a short period of term, while lump-like calculi can hardly be expelled. Ultrasonography is an accurate and reliable method of diagnosis of urinary calculus caused by melamine intake in children and it can be used as diagnostic method of choice although abdominal X-ray plain film can also visualize some of larger calculi.

Prognostic Factors of Wilms＇ Tumor Complicated with Nephroblastomatosis

Nephrogenic rests （NRs） are abnormally persistent clusters of embryonal cells, representing microscopic dysplasias of the developing kidney. NRs are found in approximately 1% of infant kidneys at autopsy. Nephroblastomatosis signifies the presence of multiple or diffuse NRs. Both NRs and nephroblastomatosis were known as precursor lesions of Wilms tumor,Nephroblastomatosis can be classified into four categories： Perilobar （PEN R only）; i ntralobar （I LNR only）; combined （PLNR and ILNR）; and universal. The diagnosis and treatment of Wilms＂ tumor have been improved constantly and achieved common sense. However, little information is available regarding Wilms＂ tumor associated with nephroblastomatosis for lower prevalence. This study aimed to investigate the prognostic factors of Wilms＇ tumor associated with nephroblastomatosis.

Clinical characteristics of hemolytic uremic syndrome secondary to cobalamin C disorder in Chinese children

Background:The present study was undertaken to investigate the clinical characteristics of hemolytic uremic syndrome(HUS)secondary to cobalamin C disorder(cbl-C disorder).Methods:We reviewed retrospectively the medical records of 3 children with HUS secondary to cbl-C disorder who had been treated between April 1,2009 and October 31,2013.Results:The 3 patients with HUS secondary to cbl-C disorder presented with progressive hemolytic anemia,acute renal failure,thrombocytopenia,poor feeding,and failure to thrive.Two of the 3 patients once had high blood pressure.The mutations of c.609G>A(P.W203X),c.217C>T(p.R73X)and c.365A>T(p.H122L)in the methylmalonic aciduria(cobalamin deficiency)cbl-C type,with homocystinuria gene were detected in the 3 patients.In these patients the levels of lactate dehydrogenase and homocysteine in serum were elevated and the level of methylmalonic acid(MMA)in urine was also elevated.After treatment with hydroxocobalamin,2 patients were discharged with no obvious abnormal growth and neurological development and 1 patient died of multiple organ failure.Conclusions:The results of this study demonstrated that cbl-C disorder should be investigated in any child presenting with HUS.The high concentrations of homocysteine and MMA could be used for timely recognization of the disease.Once the high levels of plasma homocystein and/or plasma or urine MMA are detected,the treatment with parenteral hydroxocobalamin should be prescribed immediately.The early diagnosis and treatment would contribute to the good prognosis of the disease.

Steel wire causing pseudoaneurysm of descending aorta

An l l-years-old boy presented with 7 days history of abdominal pain, precordial pain and intermittenthematemesis. The physical examination revealed appearance of anemia, precordial tenderness without other positive findings. Routine blood test was notable for Hb 60 g/L. Contrast CT scan of the chest revealed a soft tissue dense mass close to the descending aorta （Figure 1 A and B）. The mass and the adjacent artery were luminally connected and intensified substantially at the same time and to the same degree on the radiographic studies. The wall of the mass was slightly thickened and the inner surface of the wall was not smooth. The esophagus was deviated and became narrow due to compression （Figure 1 A）. Axial maximum intensity projection （MIP） showed a linear metallic foreign body （Figure I C） and local airway moved forward and became flat. Volume rendering （VR） confirmed a right- side protruding mass adjacent to the beginning of the descending aorta （Figure 1 D）. The gastroscopy showed ulceration of the esophageal mucosa （Figure 1 E）.

Detection of FOXO1 break-apart status by fluorescence in situ hybridization in atypical alveolar rhabdomyosarcoma

The morphologies of alveolar rhabdomyosarcoma(ARMS) are various. Some cases entirely lack an alveolar pattern and instead display a histological pattern that overlaps with embryonal rhabdomyosarcoma(ERMS). The method of pathological diagnosis of ARMS and ERMS has been updated in the 4th edition of the World Health Organization's guidelines for classification of skeletal muscle tumors. Under the new guidelines, there is still no molecular test to distinguish between these two subtypes of rhabdomyosarcoma(RMS). In the present study, we applied fluorescent in situ hybridization(FISH) and found that the Forkhead box O1(FOXO1) gene broke apart, amplified, and displayed an aneuploid signal that was related to the RMS pathological subtype.Aside from the fact that FOXO1 break-apart and its amplification were correlated with atypical ARMS, aneuploidies were usually found in atypical ERMS. In conclusion, our results detail a potential biomarker to improve the accuracy of pathological diagnosis by discriminating between atypical ARMS and atypical ERMS.

Surfactant protein C dysfunction with new clinical insights for diffuse alveolar hemorrhage and autoimmunity

Importance:Surfactant protein C(SP-C)dysfunction is a rare disease associated with interstitial lung disease.Early therapies may improve outcomes but the diagnosis is often delayed owing to variability of manifestations.Objective:To investigate the manifestations and outcomes of SP-C dysfunction.Methods:We retrospectively analyzed the records of five pediatric patients who were diagnosed with SP-C dysfunction between February 2014 and April 2017 at Beijing Children's Hospital.Results:The five patients included two boys and three girls with a median age at diagnosis of 1.3 years.All patients presented with interstitial lung disease and had a heterozygous SFTPC mutation,including an I73T mutation in three patients,a V39L mutation in one patient,and a Y 104H mutation in one patient.In addition to common respiratory manifestations,hemoptysis and anemia were observed in one patient with the I73T mutation.Elevated levels of autoantibodies and a large number of hemosiderin-laden macrophages in bronchoalveolar lavage fluid were found in two patients with the I73T mutation,suggesting the presence of diffuse alveolar hemorrage and autoimmunity.Chest high-resolution computed tomography features included ground-glass opacities,reticular opacities,cysts,and pleural thickening.Transbronchial lung biopsy was performed in one patient with the I73T mutation,which revealed the presence of some hemosiderin-laden macrophages in alveolar spaces.All patients received treatment with corticosteroids;two received combined treatment with hydroxychloroquine.During follow-up,the two patients who received hydroxychloroquine showed improved symptoms;of the remaining three patients,two died after their families refused further treatment,while the final patient was lost to follow-up.Interpretation:This is the first report to describe a new phenotype of diffuse alveolar hemorrhage with autoimmunity in patients with I73T SFTPC mutation.Treatment with hydroxychloroquine should be considered for patients with SP-C dysfunction.

Correlation between BRAF^(V600E) mutation and clinicopathological features in pediatric papillary thyroid carcinoma

In adults, the presence of the BRAF^(V600E) mutation in papillary thyroid cancer(PTC) has been demonstrated to be strongly associated with aggressive cancer-cell characteristics and poor patient prognosis. In contrast, the frequency of this mutation in pediatric PTC has undergone limited study, and the few available estimates range from 0 to 63%. Furthermore, the role of the BRAF^(V600E) mutation in pediatric PTC is controversial; thus, the present study aimed to investigate the prevalence and role of the BRAF^(V600E) mutation in48 pediatric patients with PTC, aged 3–13 years. Of these patients, 41 were diagnosed with classic PTC, five were found to have a follicular variant of PTC, and two to exhibit a diffuse sclerosing PTC variant. The BRAF^(V600E) mutation was identified to be present in 35.4% of the 48 analyzed patients, and in 41.5% of the patients diagnosed with classical PTC. Furthermore, the presence of the BRAF^(V600E) mutation was found to be associated with a patient age at diagnosis of less than ten years(P=0.011), the performance of a thyroidectomy(P=0.03), exhibited tumor multifocality(P=0.02) and/or extra-thyroidal invasion(P=0.003), and both a low MACIS(Metastases, Age, Completeness of resection, Invasion, Size)(P=0.036) and AMES(Age, Metastasis, Extent of tumor,Size)(P=0.001)score. Together, these data suggest that the presence of the BRAF^(V600E) mutation may be negatively correlated with partial aggressive clinicopathological features of pediatric PTC.

DICER1 mutations in twelve Chinese patients with pleuropulmonary blastoma

Our aim is to examine the impact of DICER1 mutations on the pathogenesis of pleuropulmonary blastoma(PPB) by evaluating the mutation frequency and investigating the family history of Chinese patients with PPB. The family histories of 12 children with PPB recruited consecutively were surveyed. Blood samples from patients and their first-degree relatives were tested for DICER1 mutations. Whole-genome sequencing of blood samples and formalin-fixed and paraffin-embedded(FFPE) tumor tissue was performed in one family with twins. Twelve patients with PPB included six type II and six type III cases. Seven of the12 patients harbored DICER1 mutations, six of which were frameshift or nonsense mutations. Another case carried a germline DICER1 mutation affecting the splice site. FFPE sample had a nonsense mutation in TDG and missense mutations in DICER1.In addition, two cases with DICER1 mutations were found to have lung cysts preceding the diagnosis of PPB. Furthermore, one patient had a family history remarkable for thyroid diseases. Our results indicate that the germline mutation frequency in Chinese patients with PPB is similar to the ones reported for patients from USA, UK, and Japan. Moreover, our study strongly suggests that investigating the family history and detecting germline DICER1 mutations might be of benefit to increasing awareness and improving the accuracy of the differential diagnosis of PPB from non-malignant lung cysts.

Acute myeloid leukemia following a primary mediastinal germ cell tumor

Introduction:There is a known association between primary mediastinal germ cell tumor(PMGCT)and hematologic malignancy that is not linked to treatment.They are exceptionally rare entities with a low morbidity and a poor prognosis.Case presentation:An 11-year-old boy presented with an anterior mediastinal mass diagnosed as a malignant germ cell tumor on the basis of an excisional biopsy.He was found to have acute myeloid leukemia(AML)two years after the chemotherapy for his germ cell tumor.The clinical course was very aggressive with a survival time of only 1 week after diagnosis of AML associated with PMGCT.Conclusion:AML associated with PMGCT needs to be diagnosed correctly.Relevant examinations should be carried out in patients with PMGCTs during and after chemotherapy,and long-term follow-up is still necessary to reduce the risk of morbidity and mortality.