Pediatrics International (2013) 55, e129–e132

doi: 10.1111/ped.12167

Patient Report

Anaplastic sarcoma of the kidney: Case report and literature review Noriko Watanabe,1 Daisuke Omagari,1,4 Tsutomu Yamada,1 Norimichi Nemoto,1 Takeshi Furuya,2 Kiminobu Sugito,2 Tsugumichi Koshinaga,2 Hiroshi Yagasaki,3 Masahiko Sugitani1 Departments of 1Pathology, 2Pediatric Surgery and 3Pediatrics, Nihon University School of Medicine and 4Department of Pathology, Nihon University School of Dentistry, Tokyo, Japan Abstract

Anaplastic sarcoma of the kidney (ASK) is a relatively newly recognized pediatric renal tumor. The present patient, a 13-year-old boy with a large renal mass, underwent surgery. Pathological findings showed proliferation of short spindle-shaped cells with anaplastic features including multiple foci in hyaline cartilage. Complex chromosomal abnormalities were detected in the tumor cells. Postoperative chemotherapy with the regimen for Ewing’s sarcoma achieved complete remission but the tumor recurred and the patient died during re-induction chemotherapy. Autopsy indicated the cause of death as duodenal hemorrhage. Because there were no viable tumor cells, the recurrent tumor was considered to have been completely cured by chemotherapy. ASK is a very rare tumor, of unknown pathogenesis, and no standard treatment has yet been established, but the tumor cells may be responsive to chemotherapy. Further study is needed to establish the optimal treatment strategy.

Key words anaplastic sarcoma of the kidney, autopsy, children, rare renal tumor, Wilms tumor.

Anaplastic sarcoma of the kidney (ASK) is a very rare renal pediatric tumor. Only three reports (22 cases) on ASK have been published since 2007 in the English-language journals.1–3 ASK is characterized by distinct histological features involving a spindle cell component and widespread anaplastic changes plus chondroid differentiation in most cases. The molecular pathogenesis remains unknown. We report a case of this rare tumor, including pathological, chromosomal and molecular analysis of the surgical specimen, and the disease course with autopsy findings.

Case report A 12-year-old boy was brought to a regional hospital with a complaint of hematuria. He had a medical history of spastic tetraparesis, mental retardation and epilepsy. A 3 cm-diameter mass was found in the right kidney and biopsy was performed, indicating necrotic material. He was then closely followed up. Ten months after the original presentation, at the age of 13, he developed fever and right abdominal pain. Acute appendicitis and right renal pelvic hemorrhage were diagnosed. Appendectomy and right renal pyelostomy were performed, but his condition deteriorated with right renal swelling and anemia. He was transferred to Nihon University Hospital. Computed tomography (CT) showed a 16 cm-diameter right renal tumor with heterogeneous enhancement compressing the liver and right adrenal gland. No Correspondence: Noriko Watanabe, MD, Department of Pathology, Nihon University School of Medicine, 30-1, Ohyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan. Email: [email protected] Received 28 September 2012; revised 27 March 2013; accepted 24 May 2013.

© 2013 The Authors Pediatrics International © 2013 Japan Pediatric Society

distant metastases were found. Wilms tumor (WT) with urgent oncogenic status was suspected and right radical nephrectomy was thus performed. The operative findings indicated right renal tumor with severe adhesion to the liver and retroperitoneum. Disintegration of the tumor was observed. Periaortic lymph nodes were swollen. The tumor stage was III based on the Japanese Staging System.4 The resected kidney weighed 666 g, and was wholly replaced by brownish friable tumor tissues (Fig. 1). The tumor involved the renal pelvis, ureter, adrenal gland and periaortic lymph nodes. Histologically, the tumor had dense proliferation of short spindle cells with hyperchromatic nuclei with necrotic and hemorrhagic backgrounds. Anaplastic features with bizarre enlarged nuclei and multipolar atypical mitoses were frequent (Fig. 2a). The tumor contained multifocal islands of hyaline cartilage with various atypical changes (Fig. 2b). Focal blastema-like areas with proliferation of small round cells were noted. Neither epithelial differentiation nor nephrogenic rests were detected. Immunohistochemically, the tumor cells were diffusely positive for vimentin, PGP9.5 and INI1, focally positive for CD56 and p53, highly focally positive for desmin and CD99, and negative for WT-1, actin, S-100 protein and cytokeratin. On reverse transcriptase–polymerase chain reaction assay, no fusion transcripts for ETV6-NTRK3 and STY-SSX were detected. G-banding cytogenetic analysis indicated a very complex tumor cell karyotype of 55, XY, + add (3) (q29), +del (3) (q23), +add (4) (p16), −5, add (5) (p15), add (7) (q34), add (7) (p22), add (8) (p21), −10, add (11) (p15), add (12) (p13), −13, −15, −17, −17, −19, −22, +14mar in nine of 20 tumor cells. We initially suspected diffuse anaplastic WT based on the widespread anaplastic features, but the final diagnosis was ASK, based on the pathological central review of the Japan Wilms Tumor Study.


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Fig. 1 Grossly, the kidney was wholly replaced by brownish friable tumor tissue.

Postoperative chemotherapy was initiated with regimen I for diffuse anaplastic WT,4 but was soon changed to that for Ewing’s sarcoma, a proven and promising protocol for solid refractory tumors,5 because the pathological diagnosis was changed from anaplastic WT to ASK with subsequent metastases to the lungs and liver. He was treated with combination chemotherapy regimen of ifosfamide, etoposide, vincristine, doxorubicin and cyclophosphamide (IE/VDC), consisting of ifosfamide (1800 mg/m2) and etoposide (100 mg/m2) × 5 days (week 1, 7, 15, 21 and 27), followed by vincristine (1.5 mg/m2 on day 1), doxorubicin (37.5 mg/m2 on days 1 and 2), and cyclophosphamide (1200 mg/m2 on day 1; week 4, 10, 18, 24; vincristine was omitted from weeks 18 and 24 because of paralytic ileus). The metastatic lesion became undetectable after completion of the week 18 regimen. The metastases were not irradiated, because metastatic lesions were not only in the lungs but also in the liver, such that hepatic function might have been severely impaired in the exposure field. After completion of chemotherapy, whole



Fig. 2 (a) The tumor consisted of short spindle cells arranged in a fascicular pattern with anaplastic features including bizarre enlarged nuclei and multipolar atypical mitoses. (b) Islands of hyaline cartilage indicate chondroid differentiation. © 2013 The Authors Pediatrics International © 2013 Japan Pediatric Society

abdominal irradiation was added (total 10.8 Gy) and he was discharged. Five months after discharge, however, he again complained of abdominal pain and vomiting and was readmitted. CT and magnetic resonance imaging (MRI) identified a heterogeneously enhanced 3 cm solid tumor in the right upper retroperitoneum, which showed growth with hemorrhagic lesions in only a few days. Local recurrence was suspected and the patient was treated with IE, irinotecan and a combination of topotecan and cyclophosphamide (TC). MRI performed during chemotherapy showed that the solid portion of the tumor had become cystic. In contrast, however, the patient suffered from hematemesis due to a duodenal ulcer during the course of chemotherapy. This ulcer worsened after the TC regimen and required repeated urgent endoscopic hemostasis. Platelet count ranged between 2 and 5 × 104/μL despite repeated blood transfusions. Two months after readmission, the patient died from hemorrhagic shock caused by massive hematemesis and melena. Autopsy limited to the abdominal lesion was performed. Gross and microscopic findings showed fresh erosion and scarred ulcers in the duodenum, and hematoma with a dense fibrous capsule in the right upper retroperitoneum. Even on detailed study, no viable tumor cells were detected, although a small number of degenerated atypical cells were found in the hematoma. The cause of death was considered to be duodenal hemorrhage given that the recurrent tumor had been completely cured by the re-induction chemotherapy.

Discussion Anaplastic sarcoma of the kidney was first described by Vujanic´ et al. as a newly recognized pediatric renal malignancy in 2007.1 They identified 20 cases by their distinct histological features in the three large pathological collections of the National Wilms Tumor Study Pathology Center, the International Society of Pediatric Oncology, and the United Kingdom Children’s Cancer Study Group trials (approx. 13 000 cases in total). The common histological features are a spindle cell component, widespread marked anaplastic changes and chondroid differentiation in most cases. No potentially pathogenic molecular features have been reported except for the case described by Gomi et al. with a chromosomal abnormality of 46, XX, +8, −10, der (18) t (10; 18) (q21; p11.2).3 The clinical features of this and all other reported cases are listed in Table 1. Patients ranged widely in age from 10 months to 41 years, most were female with right-sided tumors predominating, and the tumor stage was known in 18 patients, including seven stage I, five stage II, four stage III, and two stage IV cases. Diverse initial diagnoses, mostly anaplastic WT, were made. Outcomes were known in 16 patients. There were four deaths: one patient with stage I, two with stage III, and one with stage IV. With regard to differential pathological diagnosis, in the present case, based on the initial tumor presentation, the differential diagnoses included anaplastic WT, clear cell sarcoma of the kidney, rhabdoid tumor of the kidney, congenital mesoblastic nephroma, synovial sarcoma and mesenchymal chondrosarcoma. These diseases were ruled out based on overall histological features and the detection of fusion transcripts, although anaplastic

24 years/F 29 years/F 30 years/F 35 years/F 41 years/F

19 20 21 22 23



– – R

Side R R R L R L L – R R R L R

II – – – I




AWT MM Malignant mesenchymal tumor of kidney MM or anaplastic adult WT Fibrosarcoma with cartilaginous differentiation or anaplastic adult WT


Initial diagnosis MM or Rhabdomyosarcoma AWT or MM AWT AWT AWT AWT AWT AWT or MM AWT AWT AWT Sarcomatoid variant of RCC Unclassified anaplastic sarcoma with rhabdomyoblastic and cartilaginous differentiation Anaplastic mesenchymoma AWT AWT (soon revised to ASK)


N Resection


Treatment C+N N+C N+C N+C C+N+C N+C C+N+C N+C C+N+C R+N+C+R C+N+C N+C N+C+R

Relapse Unknown Unknown No No No No No Abdominal recurrence, liver metastases No Lung and bone metastases No No Preoperative lung and bone metastases decreased after treatment, no local recurrence Unknown No Lung and liver metastases, abdominal recurrence Local recurrence Lung metastases, renal tumor found postmortem No Unknown No Unknown Spine, liver and lung metastases

NED 2.5 years Unknown NED 3 years Unknown DOD 2 years

Unknown DOD 1.2 years

Unknown NED 2 years DOD 1.5 years

Outcome Unknown Unknown NED 13 years NED 14 years NED 9 years NED 9 years NED 6 years Unknown NED 7 years DOD 1.5 years NED 8 years NED 8 years NED 2.3 years

Cases 1–12,14,15,17,18,20–23 reported by Vujanic´ et al.;1 case 13 by Gomi et al.;3 case 19 by Labanaris et al.2 ASK, anaplastic sarcoma of the kidney; AWT, anaplastic Wilms tumor; C, chemotherapy; DOD, died of disease; MM, malignant mesenchymoma; N, nephrectomy; NED, no evidence of disease; R, radiation therapy; RCC, renal cell carcinoma.

15 years/F 17 years/F

13 years/F 13 years/M 13 years/M

14 15 16 (present case)

17 18

Age/Sex 10 months/F 11 months/M 1.5 years/M 3 years/F 3.3 years/F 4 years/F 4 years/M 4.3 years/M 4.8 years/M 5 years/M 8 years/F 10 years/M 12 years/F

Case 1 2 3 4 5 6 7 8 9 10 11 12 13

Table 1 Clinical features of published ASK cases

Anaplastic sarcoma of the kidney e131

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WT was difficult to exclude because of the similarity of the widespread anaplastic features of the present tumor to those of WT. Vujanic´ et al. also described anaplastic WT as being the most important tumor in the differential diagnosis of ASK and listed differences in histological features between ASK and anaplastic WT. The features of ASK are (i) absence of large areas with blastema-like cells; (ii) complete absence of epithelial differentiation; (iii) presence of highly atypical and ‘wildly’ anaplastic cells in the stroma and cartilage; and (iv) absence of WT-1 and CD56 in blastema-like foci. Vujanic´ et al. described the overall outcome of ASK as being reasonably good, considering that the patients were treated with different therapeutic protocols. If the outcomes examined are limited to patients with tumor stages III and IV, however, then three of six died, which is a high mortality rate. The present tumor was initially considered to have good responsiveness to postoperative chemotherapy, but the patient developed local recurrence and died during re-induction chemotherapy. The cause of death was hemorrhagic shock secondary to bleeding from duodenal erosion. No viable tumor cells were detected at autopsy. Considering the clinical course, the duodenal erosion would presumably have been an anticancer drug-induced mucosal injury exacerbated by thrombocytopenia. Based solely

© 2013 The Authors Pediatrics International © 2013 Japan Pediatric Society

on the response to treatment, tumor cells were apparently responsive to the chemotherapeutic regimen used. Thus, there is a possibility that the outcome of the present case would have been better had an optimal established treatment been available for ASK. It is hoped that further accumulation of cases will enable identification of the most appropriate treatment strategy.

References 1 Vujanic´ GM, Kelsey A, Perlman EJ, Sandstedt B, Beckwith JB. Anaplastic sarcoma of the kidney: A clinicopathologic study of 20 cases of a new entity with polyphenotypic features. Am. J. Surg. Pathol. 2007; 31: 1459–68. 2 Labanaris AP, Zugor V, Smiszek R, Nutzel R, Kuhn R. Anaplastic sarcoma of the kidney. Sci. World J. 2009; 9: 97–101. 3 Gomi K, Hamanoue S, Tanaka M et al. Anaplastic sarcoma of the kidney with chromosomal abnormality: First report on cytogenetic findings. Hum. Pathol. 2010; 41: 1495–9. 4 Oue T, Fukuzawa M, Okita H et al. Outcome of pediatric renal tumor treated using the Japan Wilms Tumor Study-1 (JWiTS-1) protocol: A report from the JWiTS Group. Pediatr. Surg. Int. 2009; 25: 923–9. 5 Grier HE, Krailo MD, Tarbell NJ et al. Addition of ifosfamide and etoposide to standard chemotherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone. N. Engl. J. Med. 2003; 348: 694–701.

Anaplastic sarcoma of the kidney: case report and literature review.

Anaplastic sarcoma of the kidney (ASK) is a relatively newly recognized pediatric renal tumor. The present patient, a 13-year-old boy with a large ren...
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