Primitive neuroectodermal tumour with synchronous ipsilateral clear cell carcinoma of the kidney

Abstract

We report the first case of a synchronous ipsilateral primitive neuroectodermal tumour (PNET) and clear cell renal cell carcinoma of the kidney. A 37-year-old man presented to the emergency department with a 24-hour history of colicky abdominal pain and visible haematuria. He had no relevant surgical or medical history. Physical examination was unremarkable apart from mild left flank tenderness. Triphasic CT of the abdomen and pelvis showed two solid lesions in the left kidney. Further staging CT of the chest showed no evidence of local or distal metastasis. He subsequently underwent laparoscopic radical nephrectomy. Pathological analysis of the kidney showed two synchronous renal tumours, a clear cell carcinoma and PNET of the kidney. The patient received adjuvant chemotherapy according to Ewing’s sarcoma chemotherapy protocol. Surveillance CT scans at 3, 6 and 12 months showed no evidence of disease recurrence or metastasis.

Background

Primary genitourinary sarcomas represent less than 5% of all soft-tissue sarcomas and 1%–2% of all genitourinary malignancies.¹ Of these, primary sarcomas arising from the kidney constitute less than 3% of all renal malignancies in adults and are usually diagnosed as incidental tumours. Primitive neuroectodermal tumour (PNET) arises from the neuroectoderm and presents predominantly in adolescents and young adults.² It is categorised as part of the Ewing’s sarcoma family of tumours.

Although extremely rare, genitourinary sarcomas are highly aggressive tumours with an overall 5-year cancer-specific survival (CSS) of 56% and even worse outcomes if renal in origin (5-year CSS 29%) despite multimodality treatment.³ To our knowledge, this is the first report in the literature of a patient with renal PNET (RPNET) with synchronous ipsilateral clear cell carcinoma of the kidney.

Case presentation

A 37-year-old man presented with a 24-hour history of colicky abdominal pain and visible haematuria. He had no medical, surgical or family history of significance. Physical examinations were unremarkable apart from mild left flank tenderness.

Investigations

His initial haematological and biochemical laboratory workup was normal. A triphasic CT abdomen and pelvis showed two solid enhancing lesions in the upper and lower poles of the left kidney (figures 1 and 2) but his contralateral kidney was normal. Further staging workup showed no evidence of metastatic disease.

Figure 1.

A coronal section of the CT scan showing the lower pole renal lesion which came as PNET of the kidney. PNET, primitive neuroectodermal tumour.

Figure 2.

An axial section of the CT scan showing the upper pole renal lesion which came as RCC after histology. RCC, renal cell carcinoma.

Treatment

The patient was discussed at our multidisciplinary team meeting. He underwent a left laparoscopic radical nephrectomy. Postoperative recovery was unremarkable, and he was discharged on the second postoperative day.

Outcome and follow-up

The kidney harboured two tumours (figure 3). A 33 mm extensively necrotic tan solid tumour was present in the lower pole. A 14 mm yellow solid and cystic tumour was present in the upper pole. Both tumours were confined to the kidney. The smaller tumour was a conventional clear cell renal cell carcinoma (CCRCC) on histology (figure 4), nucleolar grade 2. The larger tumour however had an unusual morphology comprising sheets of undifferentiated round to oval cells with moderate amounts of clear cytoplasm and vesicular nuclei (figure 5). There were extensive necrosis and abundant mitoses. The tumour was negative for epithelial markers (AE1/AE3, MNF116, CAM5.2, EMA, CK7 and CK20) (figure 6). It was also negative for PAX8, GATA3, RCC, AMACR, S100, melan A, HMB45, desmin, MSA, SMA, MyF4, CD117, chromogranin, synaptophysin, CDX2, TTF1, inhibin, calretinin, CD31, CD34, LCA, CD3, CD20, CD4, CD30, MPO and CD68. Negative staining with these markers excludes major morphological differential diagnoses such as RCC, epithelioid angiomyolipoma, melanoma, vascular tumours, lymphoid neoplasms, alveolar rhabdomyosarcoma, adrenal tumours, small cell carcinoma and histiocytic neoplasms. The tumour was positive for vimentin, CD56 and focally for CD10. The case was sent for expert opinion and additional analysis. Additional immunohistochemistry demonstrated strong and diffuse membranous staining for CD99 (figure 7). This was finally diagnosed as PNET, the clear cell sarcoma of kidney-like variant.

Figure 3.

Two distinct tumours are present in this nephrectomy specimen. A larger tumour is present in the lower pole and has a solid tan brown cut surface with extensive necrosis (PNET). A second smaller tumour is present in the upper pole with yellow solid and cystic cut surface (CCRCC). CCRCC, clear cell renal cell carcinoma; PNET, primitive neuroectodermal tumour.

Figure 4.

High power view of the smaller tumour which shows classical morphology of clear cell renal cell carcinoma.

Figure 5.

High power views of the larger tumour showing diffuse sheets of undifferentiated cell with moderate clear cytoplasm and vesicular nuclei.

Figure 6.

The tumour is negative for pan cytokeratin AE1/AE3.

Figure 7.

The tumour shows diffuse strong membranous staining with CD99.

This is the most common atypical variant of RPNET. It has a morphology different to classical PNET and hence different differential diagnostic considerations.

The patient was then referred to medical oncology for consideration of adjuvant chemotherapy. He underwent 14 cycles of adjuvant chemotherapy as per Ewing’s sarcoma protocol^{4 5} including vincristine, actinomycin, ifosfamide alternating with ifosfamide and etoposide.

After completion of chemotherapy, surveillance CT thorax, abdomen and pelvis imaging at 3 months, 6 months and 1 year showed no evidence of disease recurrence or progression.

Discussion

PNET was described in 1981 by Arthur Purdy Stout originating from an ulnar nerve.⁶ Embryologically, they are derived from the neuroectoderm and they can occur inside the nervous system (central tumours) or outside it (peripheral tumours). They are a member of the Ewing’s sarcoma/PNET family based on chromosomal studies. The group also includes Askin’s tumour (chest wall PNET).⁷

RPNET can affect both children and adults, however, these tumours tend to present in young age groups. The mean age at presentation is 27. The male to female ratio is 1.5:1. RPNET tends to be more aggressive than PNET at other sites with up to 50% of the cases presenting with metastasis. Preoperative diagnosis is difficult as there are no specific clinical or radiological features. Microscopically, classic PNET morphology includes small round cells and pseudorosettes reflecting its neural origin.^{8 9} It is important to differentiate this histological arrangement from other forms of RCC such as the acinar structures typical of CCRCC and the elongated trabecular growth patterns commonly seen in papillary RCC.

The diagnosis is supported by membranous staining for CD99 which is positive in over 90% of the cases. CD99 is however non-specific and can be positive, although not usually as strong or as crisp membranous, in other tumours including lymphomas and Wilms tumour.⁹ PNET is differentiated by the presence of EWST/FLI-1 fusion products detected by fluorescence in situ hybridisation in the majority of cases.

Multimodality treatment is the mainstay of management after surgical resection. The most common chemotherapy regimen is the Ewing’s sarcoma protocol and it includes vincristine, doxorubicin and cyclophosphamide alternating with ifosfamide and etoposide for approximately 14–17 cycles.^{4 5} Radiotherapy is indicated if there is local invasion or positive surgical margins.⁸

Overall RPNET is a highly aggressive tumour with poor prognosis. The 5-year survival rate had been reported as 45% to 55%. This survival rate is even less in the presence of metastasis.¹⁰

Learning points.

• Renal primitive neuroectodermal tumour (RPNET) is a highly aggressive tumour with an overall poor prognosis despite multimodality treatment.

• Diagnosis is primarily made by the immunohistopathological and molecular analysis of the specimen and often there are no characteristic clinical or radiological features allowing for preoperative diagnosis.

• To our knowledge, this is the first report of a PNET tumour of the kidney occurring with a synchronous ipsilateral renal clear cell carcinoma in the literature.