Outcome of two pairs of monozygotic twins with pleuropulmonary blastoma: case report

Zhang et al. Italian Journal of Pediatrics (2020) 46:148 https://doi.org/10.1186/s13052-020-00912-6 CASE REPORT Open Access Outcome of two pairs of monozygotic twins with pleuropulmonary blastoma: case report Shihan Zhang1, Xisi Wang1, Sihui Li2, Siyu Cai3, Tong Yu4, Libing Fu5, Na Zhang6, Xiaoxia Peng3, Qi Zeng6 and Xiaoli Ma1* Abstract Background: Pleuropulmonary blastomas (PPB) are rare aggressive paediatric lung malignancies and are among the most common DICER1-related disorders: it is estimated that 75–80% of children with a PPB have the DICER1 mutation. DICER1 mutations are responsible for familial tumour susceptibility syndrome with an increased risk of tumours. In approximately 35% of families with children manifesting PPB, further malignancies may be observed. Symptoms of DICER1 syndrome may vary, even within monozygotic twins. Preventive screening of carriers with DICER1 mutations is important and follow-up is undertaken as recommended by the 2016 International PPB Register. Case presentation: We present two pairs of monozygotic twins. In one pair of 4-year, 2-month old girls, both with DICER1 mutation, one developed PPB(II) and her identical sibling had acute transient hepatitis. In the other pair of 19month-old female babies, one had a history of bronchopulmonary hypoplasia and developed PPB(III) without DICER1 mutation, and her identical sibling had allergic asthma. Both patients with PPB were treated with R0 resection and received 12 cycles of postoperative chemotherapy. At the most recent review, the twins had been followed up for six and eight years, respectively, and they all remained healthy. However, the height and weight of the patients with PPB were lower than those of their respective identical sister. Conclusions: PPB is rare, especially in monozygotic twins. We emphasise the importance of genetic testing and follow-up in monozygotic twins with PPB. During the follow-up, children surviving PPB should be monitored closely for growth and development disorders which caused by chemotherapy. Keywords: Monozygotic twins, Pleuropulmonary blastoma, Long-term survival Background Pleuropulmonary blastoma (PPB) is a potentially aggressive, rare childhood neoplasia. It is the most common primary malignant lung tumour in children [1]. PPB is classified into three main types: type I is purely cystic; type * Correspondence: 1 Beijing Key Laboratory of Pediatric Hematology Oncology, National Discipline of Pediatrics, Ministry of Education, MOE Key Laboratory of Major Diseases in Children, Hematology Oncology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China Full list of author information is available at the end of the article II is mixed cystic and solid; and type III is an entirely solid and typically aggressive sarcoma [2]. The type of PPB correlates to the age of diagnosis and prognosis. The 5-year disease-free survival (DFS) and overall survival (OS) rates for Type I PPB are 82 and 91% respectively [3]. For Type II and Type III PPB, the 5-year DFS rate is 59 and 37%, respectively, and the 5-year OS rate is 71 and 53%, respectively [3]. A single-centre report of 41 cases with Type I, II and III PPB in our hospital revealed that the 5-year survival rate was 100, 66.7, and 66.7%, respectively, and the 5-year DFS rate was 100, 66.7 and 55.6%, respectively [4]. © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Zhang et al. Italian Journal of Pediatrics (2020) 46:148 PPB has been linked to the mutation of DICER1 as part of a predisposition syndrome for different types of tumours [5]. PPB is one of the most important causes of DICER1-associated morbidity and mortality. While it is uncommon to have more than one individual in a family diagnosed with PPB, some of the other conditions associated with a germline DICER1 pathogenic variants (e.g., nodular hyperplasia of the thyroid, benign lung cysts) may have a higher penetrance. Pathogenic germline DICER1 variants cause a hereditary cancer predisposition syndrome with a variety of manifestations [6]. The risk for most DICER1-associated neoplasms is highest in early childhood and decreases in adulthood. Current consensus guidelines for the surveillance of individuals with a DICER1 pathogenic variant suggest that chest x-ray (CXR) every 6 months from ages 0–7, and then annually from ages 8–12 [7] is vital for improving PPB prevention, surveillance, treatment and follow-up. Case presentation Case 1 As described previously [8], a girl aged 4 years and 2 months old (Twin1) was diagnosed with PPB Type II. She underwent left lower lobectomy with complete removal (R0 resection) at diagnosis and then completed 12 cycles of chemotherapy with IVADo (ifosfamide, vincristine, actinomycin D, doxorubicin) and IVA (ifosfamide, vincristine, actinomycin D), resulting in cumulative doses of ifosfamide and doxorubicin of 48 g/m2 and 240 mg/m2. No second surgery was performed. Her older sister (Twin2) developed acute transient hepatitis at about 5 years of age. Their family history showed that their mother and two aunts had thyroid nodules and their maternal grandmother died of thyroid cancer. Analysis of peripheral blood samples revealed a germline DICER1 mutation: c.C3675A (p.Y1225X) in the twins and their mother [8]. Outcome and follow-up At the most recent follow-up, the twins were about 10 years old and had been followed up for about 74 months. They remained healthy without heart, liver, kidney dysfunction and scoliosis. Twin1’s height and weight were around the 85th and 40th percentile, respectively, and Twin2’s height and weight were around the 92th and 64th percentile, respectively. Both Twin1 and Twin2 remained healthy at their last review. Follow-up imaging to monitor for pulmonary disease will include chest computed tomography (CT) for tumour recurrence and MRI for brain metastasis in Twin1. In Twin1 and Twin2, both of whom had co (...truncated)