[Multiple primary tumors in children: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.

[Adrenal cortical carcinoma in children: a clinicopathological analysis of 25 cases].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of adrenal cortical carcinoma (ACC) in children. Methods: Twenty-five children with ACC diagnosed in the Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from March 2014 to August 2022 were retrospectively analyzed. The related literature was reviewed. Results: A total of 25 children with ACC were collected, including 11 males and 14 females, with a male to female ratio of 1.0∶1.3. The patient ages ranged from 8 months to 14 years (median, 4 years). Eighteen cases with clinical data had functional tumors (18/22, 81.8%) presenting with virilization or precocious puberty (15/18), symptoms related to hypercortisolism (8/18) or endocrine symptoms mixed with both (5/18), while 3 cases (3/22, 13.6%) had unknown clinical data. The clinical manifestations of four patients with nonfunctional tumors were an abdominal mass and/or abdominal pain, walking instability and others. Grossly, the average maximum diameter of the tumor was 9.4 cm. Most of the tumors were nodular and partially encapsuled. The cut surfaces were gray or gray brown, soft with hemorrhage. Histologically, the tumor cells were diffusely distributed, separated by a vascular-rich network. The tumor cells were large, with distinct nucleoli, abundant eosinophilic or clear cytoplasm, and round or oval nuclei. The mitotic index was high, and atypical mitoses were common. Necrosis, calcification, capsule invasion or/and venous invasion were present. In some cases, the tumor invaded the surrounding soft tissues or kidneys. Immunohistochemically, the tumor cells were diffusely positive for syn and SF1 and focally positive for α-inhibin, Melan A and Calretinin, but negative for CgA. Ki-67 proliferation index ranged from 2%-90%. TP53 gene status was examined in 7 cases, in which mutations were detected in 4 cases. Follow-up data was obtained in 21 patients, among whom 18 received chemotherapy and 3 received radiotherapy. Distant metastasis occurred in 13 patients. Median progression-free survival (PFS) was 11.2 months and median overall survival (OS) was 54.7 months. Patients aged less than 5 years had a better prognosis for OS (P<0.05) than the older ones (≥5 years), but a similar PFS (P>0.05). Male patients and Ki-67 proliferation index <15% had a better prognosis tendency for OS, but there was no statistically significant difference (P>0.05). Conclusions: ACC in children is a rare, often functional tumor associated with Li-Fraumeni genetic syndrome and has a poor prognosis. Diagnosis and differential diagnosis require a combination of morphological, phenotypic and clinical analysis.

[Cloning and sequencing of a DNA fragment from Plasmodium falciparum FCC1/HN isolate].

A specific DNA fragment isolated from Plasmodium falciparum FCC1/HN isolate has been cloned in Bam H1 site of pUC18 and first partially sequenced by Sanger's method. The results show: G+C percent of DNA sequence is 26.8%, and the cloned DNA has many restriction sites which are conventional for subcloning. The authors suggest that this clone and sequence may be used as a guide for developing a DNA probe or PCR primers.

[Characterization of a surface antigen of Plasmodium falciparum merozoite with monoclonal antibody].

The monoclonal antibody (McAb) designated as C6 against erythrocytic stage of Plasmodium falciparum Fcc7801/HN showed significant growth inhibition of P. falciparum in vitro, having cross immunofluorescence reaction with P. falciparum Fcc-1/HN, Fcc7802/HN, Fcc8703/JS and P. berghei, P. cynomolgi. McAb C6 bound to the antigen distributed evenly over the entire surface of merozoites of P. falciparum, as demonstrated by immunoelectron microscopy. The McAb C6 also recognized a single protein of 71 kDa of P. falciparum by Western blotting. This antigen might be a candidate of malaria vaccine.

[DNA sequence of surface antigen gene gp195 of two Chinese isolates of Plasmodium falciparum from Hainan].

Amplification of DNA sequence of surface antigen gene, block II of gp195 from 2 Chinese isolates of Plasmodium falciparum FCC 7801/HN B3 and FCC M21/HN from Hainan, China, was established by using the polymerase chain reaction. A comparison of the 154 peptide sequences of the 2 Chinese isolates showed that they were identical, but there was a difference of 10 peptides among the established 154 peptides between the two Chinese isolates and MAD 20 (a Papua New Guinea isolate). The need to determine the fragments having protective effect against malarial infection, and to study the genetic basis of the antigen polymorphism of Chinese strains of Plasmodium falciparum is evident.

[Antigenic diversity of asexual schizont antigen GP195 of Plasmodium falciparum isolates from China].

The antigenic diversity of asexual merozoite surface antigen precursor gp195 among 6 isolates of Plasmodium falciparum from Hainan and Jiangsu provinces of China was investigated with a panel of murine anti-gp195 McAbs by indirect immunofluorescence assay and Western blotting. The results show that all isolates express certain strain-common epitopes of gp195, and at the same time express or lack some strain-specific epitopes. The 6 isolates can be divided into two major gp195 serotypes according to the reactivity patterns with the panel of anti-gp195 McAbs. Remarkable molecular weight difference in gp195 was found among 4 isolates of P. falciparum in which the Jiangsu isolate possesses a large size of gp195 (210kDa) than the other 3 Hainan isolates (less than or equal to 200kDa). The polymorphism of gp195 and it's impact on the development of antimalarial vaccine is discussed.