Case studyMetachronous anaplastic sarcoma of the kidney and thyroid follicular carcinoma as manifestations of DICER1 abnormalities☆
Introduction
Anaplastic sarcoma of the kidney (ASK) is a rare tumor first described in 2007 [1]. It mainly occurs in children and adolescents. It is histologically characterized by widespread anaplastic changes with no neoplastic epithelial structure, nephrogenic rests, or blastemal elements. Its histological similarity to pleuropulmonary blastoma (PPB) has been noted.
In 2009, germline mutations of DICER1 in familial PPB were detected in 4 families [2]. Later, DICER1 became known as the causative gene for 1 type of familial cancer syndrome presenting with increased risk of PPB, cystic nephroma (CN), thyroid tumors, ovarian Sertoli-Leydig cell tumor, and others [3]. Recently, Doros et al [4] reported 4 cases of “CN-associated renal sarcoma” with histology similar to that of PPB, detecting DICER1 mutations in 2 cases. Wu et al [5] reported 2 cases of ASK both with DICER1 germline and somatic mutations and suggested that ASK and CN-associated renal sarcoma are part of the same entity.
We previously reported a case of ASK with cystic thyroid nodules [6]. Later, this patient developed thyroid carcinoma. We suspected that this case may be an example of DICER1-related disorders and therefore performed combined sequence-based and array-based genetic analyses.
Section snippets
Materials and methods
This study was approved by the ethics boards of Kanagawa Children's Medical Center (approval no. 82-04) and the University of Tokyo (approval no. 1598-9).
Pathological features
The pathological features of the renal tumor were described previously (Fig. 1A and B) [6]. Additional examination of the cyst-like lesions showed that they were cavities within the tumor that lacked any lining; there were no true cysts. The resected right lobe of the thyroid measured 35 × 25 × 20 mm and weighed 9.8 g. On cut surface, a 20 × 20–mm grayish-white encapsulated solid mass was noted.
Histologically, the tumor was encapsulated and showed cellular growth of follicular architecture (Fig. 1C
Discussion
This is a case of metachronous ASK and TFC with a germline abnormality and independent somatic mutations in DICER1. DICER1 is an endoribonuclease central to the generation of microRNAs that repress gene expression [10]. The RNase IIIb domain is an important functional domain, which cleaves the 5p arm of the precursor microRNA from its hairpin loop. Mutations in the RNase IIIb domain have pathogenic effects in tumors because defective cleavage of 5p microRNA leads to significant reduction of its
Acknowledgment
The authors thank Ms Emiko Koyama, Ms Yukari Hasegawa, Ms Emu Kida, Mr Motohiko Tanaka, Ms Masayo Matsumura, Ms Naoko Hoshino, Ms Ki Yin, and Ms Fumie Saito for their excellent technical assistance.
References (15)
- et al.
DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma
Mod Pathol
(2014) - et al.
Anaplastic sarcoma of the kidney with chromosomal abnormality: first report on cytogenetic findings
Hum Pathol
(2010) - et al.
Substrate-specific kinetics of dicer-catalyzed RNA processing
J Mol Biol
(2010) - et al.
Anaplastic sarcoma of the kidney: a clinicopathologic study of 20 cases of a new entity with polyphenotypic features
Am J Surg Pathol
(2007) - et al.
DICER1 mutations in familial pleuropulmonary blastoma
Science
(2009) - et al.
DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome
J Med Genet
(2011) - Wu, M K, Druker H, Thorner H, et al. DICER1 mutations occurring in childhood anaplastic sarcoma of kidney. American...
Cited by (13)
Diagnostic Pathology: Pediatric Neoplasms
2018, Diagnostic Pathology: Pediatric NeoplasmsAnaplastic sarcoma of the kidney in children: a clinicopathological and genetic characteristics analysis of five cases
2023, Chinese Journal of PathologyAnaplastic Sarcoma of the Kidney With Heterologous Ganglioneuroblastic Differentiation: Another DICER1-Associated Tumor
2022, Pediatric and Developmental PathologyIntrathyroidal Thymus (Incidentaloma) Mimicking Thyroid Neoplasia in DICER1 Syndrome
2021, European Thyroid Journal
- ☆
Disclosures: The authors have no financial relationship and no funding to disclose.