Clinical Characteristics and Image Manifestations of a Rare Retinoblastoma with a Bone Metastasis.

Purpose: Retinoblastoma (RB) is the most common intraocular malignancy in infancy and childhood. This study evaluated the clinical and imaging features, treatment, and prognosis of patients with recurrent RB with limb bone metastases and without central nervous system involvement. Patients and Methods: The clinical data of five patients with RB with limb bone metastases who were diagnosed at the Department of Pediatrics in Beijing Tongren Hospital between January 2015 and January 2021 were analyzed retrospectively. Results: Three males and two females were included (seven eyes: four group E and one each of group D, C, and B). The most common symptom was pain. Three patients had bone marrow and lymph node metastases. Three patients had single and two had multiple skeletal lesions. The main bones that were involved were the femur, humerus, talus, and ulna. The simultaneous involvement of the bone marrow and cortex was also observed. Serum neuron-specific enolase (NSE) levels were significantly elevated in four cases and slightly elevated in one case; primary intravenous chemotherapy resulted in a decrease in NSE levels and the gradual resolution of the bone lesions. Two patients died at the time of follow-up and three were in complete remission. The results of the statistical analysis showed that anterior chamber invasion was correlated with prognosis, and there was significant difference in the decrease in the serum NSE levels after intravenous chemotherapy. Conclusion: Regular lifelong follow-up of patients with RB is warranted to identify bone metastases earlier. Anterior chamber invasion may be a risk factor. The simultaneous involvement of the bone marrow and cortex is characteristic manifestations in images of RB with bone metastases. Multidisciplinary treatment especially intravenous chemotherapy is useful, at least at the beginning.

Correlation between Family RB1 Gene Pathogenic Variant with Clinical Features and Prognosis of Retinoblastoma under 5 Years Old.

Retinoblastoma (RB) is the most common primary intraocular malignant tumor in infants and the prototype of human hereditary tumors. Its occurrence and development are closely related to the pathogenic variant of tumor suppressor RB1 gene. We aim to analyze the characteristics of RB1 gene pathogenic variant and clinical phenotype in retinoblastoma patients and their relatives. Children with RB were recruited from August 2007 to November 2017. QT-PCR, probing, and gene sequencing were used to analyze the sequence of RB1 gene in RB children, their parents, or grandparents with a clear history of illness. The SPSS20.0 software was used to analyze the correlation between polymorphisms of RB1 gene and the incidence and prognosis of the enrolled children and relatives. 40 RB children (20 males and 20 females) were recruited, unilateral RB accounted for 52.5% (21/40), bilateral RB accounted for 42.5% (17/40), and trilateral RB accounted for 5.0% (2/40). 6 patients had a clear family history (15.0%, 6/40). It had been verified that 19 probands (47.5%) have RB1 gene pathogenic variants (11 frameshift and 8 missense pathogenic variants), of which germline inheritance accounted for 47.4% (9/19) and nongermline heredity accounted for 52.6% (10/19). Pathogenic variants of 10 nucleic acid sites without reported were found, among which c.2455C>G (p.L819V) was confirmed to have heterozygous pathogenic variants in both a bilateral RB patient and his mother with unilateral RB. Family genetic high-risk factors, bilateral/trilateral RB, >12-month-onset RB have a higher proportion of RB1 gene pathogenic variant than children with no family history, unilateral RB, and ≤12-month (P = 0.021, 0.001,0.034). The proportion of pedigree inheritance of infantile retinoblastoma with bilateral disease is high. There was a certain proportion of RB1 gene pathogenic variant in 3-5-year-old children with bilateral RB, even if they had no family genetic history. Therefore, the detection of RB1 gene pathogenic variant should not only focus on infants but also on the phenotype of RB1 gene pathogenic variant in children over 3 years old with bilateral eye disease.

Clinical features and imaging manifestations of retinoblastoma with hepatic metastasis.

Clinical data of five patients with hepatic metastases of retinoblastoma were analyzed retrospectively (two had bilateral tumors three had unilateral intraocular tumors). On computed tomography, multiple and single low-density foci were observed. Four patients had tumor remission, and one showed no response after chemotherapy. Three patients who underwent enucleation were at high risk for extensive choroidal invasion. Central nervous system and bone metastases occurred in all five patients. Neuron-specific enolase and lactate dehydrogenase levels were significantly elevated in all patients. Two patients died (not from hepatic metastasis). Three patients (one with tumor progression and two with shorter courses) are continuing treatment.

Case report: Delayed retinoblastoma relapse in a lymph node after 9 years of complete remission.

Retinoblastoma (RB) is the most common primary intraocular malignancy of childhood. Recurrence of RB often occurs within 6 months to 1 year after the end of treatment. Orbital tissue is the most common site of recurrence in children who have undergone enucleation; other sites include the central nervous system, bone, bone marrow, lymph nodes, and other organs. Here, we describe an adolescent girl who presented with RB recurrence and metastasis in a distant lymph node after 9 years of complete remission. The tumor was an incidental finding during a routine examination and was misdiagnosed as lymphadenitis. After histopathologic examination of an aspiration biopsy sample, the correct diagnosis of recurrent metastatic RB was made. Systemic chemotherapy and surgical excision were provided; the patient remained tumor-free during the 6-month follow-up period. RB often relapses within 1 year after treatment; orbital tissue is the most common site of recurrence. However, our patient's case was unique in terms of delayed relapse and the presence of a single metastatic site; these findings may provide new insights into the behavior of RB. Furthermore, this case report indicates the need for lifelong follow-up of children with RB. Oncologists should be vigilant when treating patients with a history of RB, because complete remission does not mean complete safety; long-term recurrence and metastasis may occur. Lifelong follow-up is necessary for children with RB. Complete remission might be achieved after active and standardized treatment.

Low miR-210 and CASP8AP2 expression is associated with a poor outcome in pediatric acute lymphoblastic leukemia.

The prognostic significance of microRNA (miR)-210 and the caspase 8-associated protein 2 (CASP8AP2) gene in children with acute lymphoblastic leukemia (ALL) has been validated and CASP8AP2 has been demonstrated as a target of miR-210. In the present study, the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine miR-210 and CASP8AP2 expression in 91 children with ALL. Associations between gene expression levels and the prognostic value of combined detection of the two indicators were analyzed. Results from a receiver operating characteristic curve demonstrated that threshold values of miR-210 and CASP8AP2 were 3.8243 and 0.4760, respectively. Although the expression of miR-210 and CASP8AP2 were not associated at the mRNA level in pediatric ALL, combined detection of the two predicted ALL prognosis with an increased accuracy. Furthermore, an equation was devised including minimal residual disease at day 33 and expression of miR-210 and CASP8AP2, which may enable bone marrow relapse to be predicted more precisely compared with the current risk stratification.

[Prognostic Significance of Joint Detection of miR-210 and Minimal Residual Disease in Pediatric Acute Lymphoblastic Leukemia].

OBJECTIVE: To detect the expression of microRNA-210(miR-210) in childhood acute lymphoblastic leukemia(ALL), and to evaluate the role of the joint detection of miR-210 and MRD in the prognosis and clinical treatment of pediatric ALL. METHODS: Eighty-eight children diagnosed with ALL were included in the study. miR-210 was quantitatively detected by real-time quantitative polymerase chain reaction(RQ-PCR) in 88 ALL patients. The average Ct value of samples obtained from 5 pediatric ALL patients with long-term complete continuous remission (CCR>5 years) was used as a calibrator. The expression levels of miR-210 in newly diagnosed patients was calculated by the 2-ΔΔCt method and presented as multiple changes compared with that of the 5 CCR patients. RESULTS: The expression of miR-210 in the favorable prognosis group was significantly higher than that in the unfavorable prognosis group (10.64±1.5 vs 3.27±0.68)(P<0.05). Compared with the miR-210 high-expression group, poorer relapse-free survival(RFS), event-free survival(EFS) and overall survival(OS) (P all <0.001) were found in the low-expression group. Based on the expression of miR-210 and MRD, the 88 cases were divided into 3 groups. The relapse rate of miR-210-MRD high-risk group (70%) was significantly higher than that of the miR-210-MRD middle-risk group(6.25%) and miR-210-MRD low-risk group (2.1%). Kaplan-Meier survival analysis demonstrated that the miR-210-MRD high-risk group had poorer RFS, EFS and OS than those in other 2 groups (P all <0.01). CONCLUSION: The expression level of miR-210 is an independent prognostic factor for pediatric ALL, and the miR-210 is a good useful indicator for predicting the relapse and induction failure of childhood ALL. Joint detection of miR-210 and MRD can help predict outcomes more precisely, thus may be used as an effective mean of determining prognosis, monitoring recurrence, and guiding treatment.

A single-center retrospective study of pediatric hepatoblastoma.

Hepatoblastoma is a malignant liver tumor generally diagnosed in infants and children <3 years old. The current retrospective study aimed to investigate the associations of tumor stage, pathological type, metastasis and chemotherapy with clinical outcomes. In the current study, a total of 102 patients with hepatoblastoma were enrolled between September 2006 and June 2014. Clinical records and follow-up information for each of patient were obtained to conduct a Kaplan-Meier survival analysis and log-rank test. The median age of the subjects was 1.5 years, and 98 patients had stage III or IV hepatoblastoma. Complete or partial remittance occurred in 72 subjects, and 91 underwent surgical operation. The survival rate differed significantly among patients with different tumor stages (P=0.015, χ2=8.359). The mortality rate of stage IV subjects with intrahepatic metastasis was significantly higher than that of those without (P=0.004). Among the 45 subjects with relapsed hepatoblastoma, the mortality rate was higher in the subjects that abandoned chemotherapy than in patients who continued regular chemotherapy. In total, 27 of 45 subjects with relapsed hepatoblastoma succumbed to the disease; 20 of them abandoned chemotherapy treatment; and the remaining 7 patients underwent regular chemotherapy and succumbed to the disease by the end of follow-up. The present study indicates that the increased mortality rate was associated with postoperative residual-induced intrahepatic metastasis and relapsed hepatoblastoma; and that regular chemotherapy is necessary for patient to achieve complete or partial remission following surgical operation.

Clinical efficacy and prognosis factors for advanced hepatoblastoma in children: a 6-year retrospective study.

OBJECTIVE: This study aimed to investigate the effect of multimodality treatment of advanced paediatric hepatoblastoma (HB) and the factors affecting prognosis. METHODS: A total of 35 children underwent multimodality treatments consisting of chemotherapy, surgery, interventional therapy, and autologous peripheral blood stem cell transplantation. The patients were followed up every month. RESULTS: Serum AFP levels in 33 out of 35 patients in this study were significantly increased (P = 0.0002). According to the statistical scatter plot, the values of serum AFP on the 25th, 50th, and 75th percentages were 1,210, 1,210 and 28,318 ng/dl, respectively. Of the 35 cases, 21 were stage IV. 18 cases were treated with systemic chemotherapy before surgery, and 3 cases with locally interventional chemotherapy before surgery. Statistical analysis showed that the preferred interventional treatment affected prognosis, and that there was a statistically significant difference (P = 0.024). Some 33 patients completed the follow-up, of which 17 were in complete remission (CR), 5 were in partial remission (PR), 1 became disease progressive (DP) , and 10 died. The remission and overall survival rates were 66.7% (22/33) and 69.7% (23/33), respectively. Patients with the mixed HB phenotypes had worse prognoses than the epithelial phenotype (P < 0.001), and patients in stage IV had a lower survival rate than those in stage III (P < 0.001). CONCLUSION: Multimodality treatment can effectively improve remission rate and prolong the survival of children with advanced HB. In addition, alpha-fetoprotein (AFP), a tumor marker of liver malignant tumors, HB pathological classification, and staging are highly useful in predicting prognosis.

Study on clinical therapeutic effect including symptoms, eye preservation rate, and follow-up of 684 children with retinoblastoma.

INTRODUCTION: Retinoblastoma is the most common type of primary malignant intraocular tumor in children. The purpose of this study is to summarize the clinical experience of diagnosis and treatment for retinoblastoma, aiming to provide appropriate knowledge for surveillance and therapy for retinoblastoma. METHODS: We performed retrospective analysis of 684 children (885 eyes) with advanced retinoblastoma diagnosed in the department of Pediatrics in Tongren Hospital, Beijing, China, between September 2005 and May 2010. RESULTS: The average age at first diagnosis was 2.2 ± 1.7 years with overall median age 1.91 years. Leucocoria was the most common sign at the initial diagnosis (70.47%, 482/684). A total of 21 cases (3.06%) had positive family history. According to International Retinoblastoma Classification, 551 cases (80.57%, 723 eyes) were A-E stage and 81.47% (589/723) were D-E stages of retinoblastoma; extraocular stage was present in 101 cases (120 eyes, 14.76% ); metastatic stage was present in 32 cases (44 eyes, 4.67%). Pathology diagnosis was performed in 494 cases of unilateral or bilateral enucleation; 91 cases were grade I, 260 cases were grade II, 94 cases were grade III, 49 cases were grade IV. The median follow-up time was 27 months until June 2010. Total survival rate was 95.13%. A total of 34 cases were lost to follow-up and 34 cases were abandoned. CONCLUSIONS: Children developed retinoblastoma at a young age. Early diagnosis is difficult. Key factors of clinical treatment and long survival rate were diagnosis and treatment at the early stage with multidisciplinary methods.

[Therapeutic effects of high dose chemotherapy combined with autologous peripheral blood stem cell transplantation for neural ectodermal solid tumor originated from neural crest in children].

OBJECTIVE: To investigate the efficacy of high dose chemotherapy combined with autologous peripheral blood stem cell transplantation (APBSCT) for the treatment of neural ectodermal solid tumor originated from neural crest in children. METHODS: Twenty-three children at a medium age of 5.8 + or - 3.5 years with neural ectodermal solid tumor originated from neural crest were enrolled. Of the 23 children, 20 with stage IV neuroblastoma (9 were in complete remission, 7 were in partial remission and 4 were in progressive disease), 2 with stage IV primitive neuroectodermal tumor (PNET) in complete remission, and 1 with retinoblastoma in partial remission. Before APBSCT the children received 8.0 + or - 4.3 courses of chemotherapy. During chemotherapy the autologous peripheral blood stem cells were harvested and the tumor excision was performed. Then APBSCT was performed. RESULTS: The reconstruction of the hematopoietic system was noted in 19 of 20 children with stage IV neuroblastoma 16.5 + or - 0.9 days after transplantation. A follow-up (median 15.8 months) was done in these children. The follow-up showed that the survival rate in children in complete remission before transplantation was 100%, 57% in those in partial remission, and none of children in progressive disease survived (P<0.05). The total survival rate was 67% in children with neuroblastoma. The child with retinoblastoma had complete remission in a 6-months follow-up. The tumors recurred in children with PNET 5 to 8 months after transplantation and all died within one year after transplantation. CONCLUSIONS: High dose chemotherapy combined with APBSCT can result in a good outcome in children with neural ectodermal solid tumor originated from neural crest in complete remission before transplantation and can improve the outcome in patients in partial remission before transplantation. However, the children with PNET, even in complete remission before transplantation, do not respond to the therapy.