Elsevier

Human Pathology

Volume 61, March 2017, Pages 205-209
Human Pathology

Case study
Metachronous anaplastic sarcoma of the kidney and thyroid follicular carcinoma as manifestations of DICER1 abnormalities

https://doi.org/10.1016/j.humpath.2016.06.024Get rights and content

Summary

Anaplastic sarcoma of the kidney (ASK) is a tumor found in the pediatric age group and shows many histopathological similarities to pleuropulmonary blastoma (PPB). We present a 12-year-old girl diagnosed with ASK and, 3 years later, with thyroid follicular carcinoma (TFC) with DICER1 abnormalities. Germline insertion/deletion (p. G1809_S1814delinsA) and independent somatic mutations (p. E1705K in ASK, p. E1813D in TFC) were identified. All of these abnormalities are in the catalytic domain of RNase IIIb. Single-nucleotide polymorphism genotyping microarray revealed independent copy number alterations (trisomy 8, monosomy 10, loss of 17p, and partial gain of 17q in ASK; trisomy 5 and partial loss of Xq in TFC). The copy number alteration pattern of ASK was similar to the pattern previously reported in PPB. The present case implies that ASK is a renal counterpart of PPB and that ASK with DICER1 abnormalities should be suspected in a broader age group than PPB.

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.

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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)

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Disclosures: The authors have no financial relationship and no funding to disclose.

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