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  Table of Contents  
Year : 2016  |  Volume : 53  |  Issue : 1  |  Page : 109-112

Primitive neuroectodermal tumors of kidney: Our experience in a tertiary care center

1 Department of Urology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication28-Apr-2016

Correspondence Address:
A Seth
Department of Urology, All India Institute of Medical Sciences, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-509X.180854

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 » Abstract 

Objectives: Primitive neuroectodermal tumors (PNET) are rare highly aggressive neoplasms. The diagnosis is made by histopathology with the support of immunohistochemistry (IHC) and cytogenetics. The aggressive multimodality treatment is recommended for the management of these tumors. The purpose of our study is to review our experiences in the diagnoses and treatment of PNET of the kidneys. Materials and Methods: We retrospectively reviewed the data of all the patients, who were treated for the PNET of the kidneys at our institute between April and March 2011 and compared with the available literature. Results: A total of eight patients were treated for PNET of the kidney. Out of the eight patients, four were males and four females. Nearly 50% of our patients had inferior vena caval thrombus at the time of presentation. The diagnosis was made on histopathology supported by IHC. Out of the eight patients, one patient had intraoperative death due to massive pulmonary thromboembolism and another died on the 7th post-operative day due to disseminated intravascular coagulation and multiorgan failure. Rest six patients were treated with post-operative chemotherapy or a combination of chemotherapy and radiotherapy. For these six patients, overall median survival was 45 months with a 3 year disease-free survival of 66% and 5 year survival of 44%. Conclusions: PNET of the kidneys are rare peripheral neuroectodermal tumors with an aggressive clinical course. These tumors carry a very poor prognosis. An aggressive treatment approach using a combination of surgery, chemotherapy and radiotherapy is recommended for a reasonable survival in these tumors.

Keywords: Chemotherapy, primitive neuroectodermal tumors, radiotherapy, surgery, vena caval thrombus

How to cite this article:
Seth A, Mahapatra S K, Nayak B, Saini A K, Biswas B. Primitive neuroectodermal tumors of kidney: Our experience in a tertiary care center. Indian J Cancer 2016;53:109-12

How to cite this URL:
Seth A, Mahapatra S K, Nayak B, Saini A K, Biswas B. Primitive neuroectodermal tumors of kidney: Our experience in a tertiary care center. Indian J Cancer [serial online] 2016 [cited 2021 Aug 3];53:109-12. Available from: https://www.indianjcancer.com/text.asp?2016/53/1/109/180854

 » Introduction Top

Primitive neuroectodermal tumors (PNET) are malignant, small round cell tumors (RCTs), which commonly develop in bone and soft-tissue of the body.[1] Rarely have they been found in other parts of the body, such as the kidney, bladder, prostate, testis, ovary and uterus, etc.[2],[3],[4],[5] PNET of the kidney are very rare malignant neoplasms. They were first recognized by Stout in 1918.[6] Because of the similarity of PNET to Ewing's tumor, it is difficult to estimate their exact number.[7] Until date, about 50 cases have been reported in the literature. These tumors frequently arise in childhood and adolescence with an aggressive clinical course.[8] Clinical manifestations are similar to other renal neoplasms. The diagnosis is generally made by histopathology. PNET of the kidney carry a poor prognosis due to their higher rate of local recurrence and early metastases.[9] There have been isolated case reports of the inferior vena cava (IVC) thrombus in PNET of the kidney. In this present work, we share our experience with PNET of the kidney and present the largest series of IVC thrombus in these patients.

 » Materials and Methods Top

Between April 2005 and March 2012, a total of 382 patients underwent radical nephrectomy at our institute, with 48 of these patients having IVC thrombus. Out of this total, eight patients were diagnosed with PNET of the kidney, with four of these patients having IVC thrombus. A case report of two patients with PNET of the kidney has been published by our institute in 1995.[8] However, due to lack of follow-up, those two patients are not included in the current series. All patients were evaluated pre-operatively by history, physical examination, complete blood count, liver and renal function tests, chest X-ray and contrast enhanced computerized tomogram (CECT) of the abdomen and pelvis. In four patients with IVC thrombus detected in the CECT of the abdomen [Figure 1], ultrasound Doppler was performed to determine the extent of the thrombus. In one patient with intra-cardiac thrombus, transesophageal echocardiogram was done before surgery. All patients were managed with surgery and chemotherapy, with or without radiotherapy. Surgical treatment included radical nephrectomy with regional lymphadenectomy with IVC thrombectomy in patients having caval thrombus [Figure 2]. All patients were followed-up regularly with physical examinations, complete blood counts, liver function tests, chest X-rays and CECT of the abdomen and pelvis. Survival was calculated by the Kaplan-Meier method and statistical analysis was performed using the log-rank test (Statistical Package for the Social Sciences 11.5 SPSS Inc. 233 South Wacker Drive, 11th floor Chicago IL 60606-6412) for prognostic factor analysis.
Figure 1: Contrast enhanced computerized tomogram abdomen of a patient showing renal tumor with inferior vena caval thrombus with intrahepatic extension

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Figure 2: Intraoperative picture demonstrating inferior vena cava, left renal vein and tumor thrombus

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 » Results Top

Of the eight patients with renal PNET, four were male and four were female. The average age of the patients was 33.5 years and the median age of the presentation was 27.5 years. The most common presenting complaints among the patients were abdominal pain, abdominal mass and hematuria. Two of the patients had enlarged lymph nodes and four patients had IVC thrombus. One patient presented with  Budd-Chiari syndrome More Details with hepatomegaly, ascites and jaundice. As a palliative measure, this patient was subjected to angioembolization and fine-needle aspiration cytology was performed and diagnosed as PNET. Patient received 12 cycles of neoadjuvant chemotherapy with partial response. Age, sex, mode of presentation, staging and treatment received, post-operative complication and survival are summarized in [Table 1].
Table 1: Clinical Presentations and treatment details

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All patients underwent radical nephrectomy. Lymphadenectomy were performed on two patients with regional lymph node enlargement. The four patients with IVC thrombus underwent IVC thrombectomy. In one patient, IVC thrombectomy was performed under deep hypothermic circulatory arrest. The same patient developed disseminated intravascular coagulation (DIC) and multi-organ failure in the post-operative period and died. The diagnoses were confirmed after histopathology supported by immunohistochemistry (IHC) [Figure 3] and [Figure 4].
Figure 3: Renal primitive neuroectodermal tumors composed of small round cells with Homer-Wright rosettes in the tumor

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Figure 4: Tumor cell showing diffuse nuclear immunopositivity for CD99 (macrophage inhibitory cytokine 2 product)

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The six patients who survived the immediate post-operative period received chemotherapy in the post-operative period. The chemotherapeutic drugs used were vincristine (V), adriamycin (A), cyclophosphamide (C), ifosphamide (I) and etoposide (E). The patients received alternate cycles of vincristine, adriamycin and cyclophosphamide (VAC) and IE 3 weekly for total 16 courses. The doses of chemotherapeutic drugs used were as follows: 2 mg/m 2 of vincristine, 75 mg/m 2 bolus infusion of adriamycin and 1200 mg/m 2 of cyclophosphamide. The doses for ifosphamide and etoposide were as follows: 1800 mg/m 2 of ifosphamide per day for 5 days and 100 mg/m 2 of etoposide per day for the same 5 days. Out of six patients who survived after surgery, two patients with positive lymph nodes (as determined by CECT of the abdomen) received adjuvant radiotherapy.

The mean follow-up in our series was 42 months, with a range of 14-62 months. Of six patients who were disease-free after primary surgery and who had completed treatment, three were living and disease-free at last follow-up. The other three patients had relapsed at either local and/or distant sites (one in renal bed and two in the liver) during varying periods of follow-up. Overall median survival was 45 months, with a 3 year disease-free survival of 66% and 5 year survival of 44% as summarized in [Graph 1].

 » Discussion Top

PNET of the kidney is an extremely rare renal neoplasm with neural crest origin. It is a member of the family of small RCTs.[6] Since it has not been differentiated from Ewing's sarcoma, an accurate estimate of the number of kidney PNET is not possible.[7] Renal PNET is more aggressive than PNET of other locations. Due to its rarity, the exact clinical outcome is not well defined in the literature.

It usually presents during childhood and adolescence.[8] The average at diagnosis was 27.7 years in a review by Kuroda et al.[10] The average age of presentation in our series was 33.5 years, with the median age being 27.5 years. Its presentation is similar to other renal tumors. Most common presentations are abdominal pain, abdominal mass and hematuria. In our series, all patients presented with abdominal pain and abdominal mass. In contrast to other series in which the patients were either organ confined or metastatic at presentation, 50% of our patients had IVC thrombus at the time of presentation.[1],[11]

There are no specific radiological findings to diagnose PNET of the kidney pre-operatively. Radiologically, PNETs are large tumors with lack of parenchymal infiltration, with diffuse large calcification, along with areas of necrosis, hemorrhage and higher peripheral vascularity.[12] The diagnosis is often made after surgery and is typically made by histopathology supported by IHC and cytogenetics. Microscopically, PNET of the kidney are small to medium sized monomorphic round cells with hyperchromatic nuclei and minimal cytoplasm arranged in loose cohesive sheets. Though the presence of Homer Wright rosettes is less common in extra-osseous Ewing's sarcoma, their presence is a sure/reliable diagnosis of PNET. The diagnosis is often confirmed by IHC and cytogenetics. The reactivity to vimentin, neuron specific enolase and S-100 may help in making the diagnosis, but their presence is not pathognomonic. The presence of macrophage inhibitory cytokine 2 gene product, CD99, confirms the diagnosis.[12],[13] In our series, diagnoses were confirmed in all cases with IHC.

PNET of the kidney is a highly aggressive tumor with a poor prognosis. It has a high tendency for local recurrence and metastasis at an early stage. Surgery is the most important aspect of the management. Before the routine use of chemotherapy, the 5 year survival rate in these patients was lesser than 10%. However, with multimodality treatment using surgery, chemotherapy and radiotherapy, survival can be improved in these patients. The overall 5 year disease specific survival rate of organ confined disease is around 45-55%.[7] The standard chemotherapeutic agents recommended in these patients are VAC. However, etoposide (E) and ifosfamide (I) have been recently added to the previous lists. The initial chemotherapy protocol for PNET was the RCT II protocol. An RCT II protocol includes 2 mg/m 2 of vincristine, 75 mg/m 2 bolus infusion of adriamycin and 1200 mg/m 2 of cyclophosphamide.[11] With the addition of etoposide and ifosphamide to the VAC regimen, the current standard chemotherapy protocol for PNET has been that for Ewing's family of tumors, (EFT)-2001. In the EFT-2001 protocol, 1800 mg/m 2 of ifosphamide per day for 5 days and 100 mg/m 2 of etoposide per day for the same 5 days are added to the VAC regimen.[11] However in our institute, we have used an alternate cycle of VAC and IE 3 weekly for total 16 courses. The total duration of chemotherapy was 48 weeks.

In our series, 0.02% of renal mass were diagnosed as PNET and 12.5% had IVC thrombus. As ours is the premier government institute of the country and all complex cases are referred to our institute from all peripheral centers, there is a higher incidence of IVC thrombus in our series when compared with other series reported in the literature.[14],[15] Only isolated case reports of renal PNET with IVC thrombus have been presented in the literature.[16],[17] Thyavihally et al. reported renal PNET with IVC thrombus in only one patient in a series of 16 patients.[11] In our series, 50% of patients presented with IVC thrombus. To the best of our knowledge, this is the largest reported series of PNET patients with IVC thrombus. The subjective impression of the operating surgeon, who performed the largest number of IVC thrombus in our series, was that the tumor thrombus in these four PNET patients was significantly more friable than other IVC thrombus. A massive thromboembolism resulting from dislodgement of the tumor thrombus was the cause of death of the patient who died in the intraoperative period. The other patient who died on the 7th post-operative day, due to disseminated DIC and multi-organ failure, had level IVC thrombus invading the wall of IVC, necessitating IVC resection.

The overall 5 year disease-free survival rate for organ confined renal PNET is around 45% to 55%.[7] The median relapse-free survival of advanced disease in another reported series was only 2 years.[18],[19] Most patients with advanced renal PNET die of progressive disease within 1 year of diagnosis.[20] Thyavihally et al. demonstrated a median survival of 40 months, with 3 year and 5 year disease-free survival rates of 60% and 42%, respectively.[11] In our series, excluding the two deaths in the perioperative period, the six patients were managed aggressively with multimodal treatment. The overall median urvival was 45 months, with a 3 year disease-free survival of 66% and 5 year survival of 44%. The small number of patients with renal PNET in our series limits any statistical comparisons of treatment outcomes. However, with a dedicated and sincere focus on treatment schedule and with the use of multimodal treatment in a tertiary center like ours, survival can be improved in these patients.

 » Conclusion Top

PNET of the kidneys are extremely rare peripheral PNET having neural crest origin. They have an aggressive clinical course with poor prognosis. PNET of the kidney should be kept in mind whenever a large renal tumor is present in adolescents and young adults. The IVC tumor thrombus in these cases is more friable and always has a propensity for intraoperative dislodgement. Due to its rarity of the disease, there is no standard guideline regarding its management. Aggressive multimodality treatment can improve the survival of these patients in a tertiary center where both the facility and expertise are available.

 » References Top

Rodriguez-Galindo C, Marina NM, Fletcher BD, Parham DM, Bodner SM, Meyer WH. Is primitive neuroectodermal tumor of the kidney a distinct entity? Cancer 1997;79:2243-50.  Back to cited text no. 1
Seemayer TA, Thelmo WL, Bolande RP, Wiglesworth FW. Peripheral neuroectodermal tumors. Perspect Pediatr Pathol 1975;2:151-72.  Back to cited text no. 2
Desai S. Primary primitive neuroectodermal tumour of the urinary bladder. Histopathology 1998;32:477-8.  Back to cited text no. 3
Peyromaure M, Vieillefond A, Boucher E, De Pinieux G, Beuzeboc P, Debré B, et al. Primitive neuroectodermal tumor of the prostate. J Urol 2003;170:182-3.  Back to cited text no. 4
Rose PG, O'Toole RV, Keyhani-Rofagha S, Qualman S, Boutselis JG. Malignant peripheral primitive neuroectodermal tumor of the uterus. J Surg Oncol 1987;35:165-9.  Back to cited text no. 5
Stout AP. A tumor of the ulnar nerve. Proc NY Pathol Soc Proc NY Pathol Soc 1918;18:2-12.  Back to cited text no. 6
Casella R, Moch H, Rochlitz C, Meier V, Seifert B, Mihatsch MJ, et al. Metastatic primitive neuroectodermal tumor of the kidney in adults. Eur Urol 2001;39:613-7.  Back to cited text no. 7
Gupta NP, Singh BP, Raina V, Gupta SD. Primitive neuroectodermal kidney tumor: 2 case reports and review of the literature. J Urol 1995;153:1890-2.  Back to cited text no. 8
Romero FR, Rais-Bahrami S, Muntener M, Permpongkosol S, Fine SW, Paidas CN, et al. Metastatic primitive neuroectodermal tumor to the kidney. Urol Int 2007;78:286-8.  Back to cited text no. 9
Kuroda M, Urano M, Abe M, Mizoguchi Y, Horibe Y, Murakami M, et al. Primary primitive neuroectodermal tumor of the kidney. Pathol Int 2000;50:967-72.  Back to cited text no. 10
Thyavihally YB, Tongaonkar HB, Gupta S, Kurkure PA, Amare P, Muckaden MA, et al. Primitive neuroectodermal tumor of the kidney: A single institute series of 16 patients. Urology 2008;71:292-6.  Back to cited text no. 11
Jimenez RE, Folpe AL, Lapham RL, Ro JY, O'Shea PA, Weiss SW, et al. Primary Ewing's sarcoma/primitive neuroectodermal tumor of the kidney: A clinicopathologic and immunohistochemical analysis of 11 cases. Am J Surg Pathol 2002;26:320-7.  Back to cited text no. 12
Marley EF, Liapis H, Humphrey PA, Nadler RB, Siegel CL, Zhu X, et al. Primitive neuroectodermal tumor of the kidney – Another enigma: A pathologic, immunohistochemical, and molecular diagnostic study. Am J Surg Pathol 1997;21:354-9.  Back to cited text no. 13
Campbell SC, Novick AC, Bukowski RM Campbell SC, Novick AC, Bukowski RM. Renal tumors. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA, editors. Campbell-Walsh Urology. 9th ed. Philadelphia: Saunders-Elsevier; 2007. p. 1567-637.  Back to cited text no. 14
Mootha RK, Butler R, Laucirica R, Scardino PT, Lerner SP. Renal cell carcinoma with an infrarenal vena caval tumor thrombus. Urology 1999;54:561.  Back to cited text no. 15
Nerli RB, Hiremath MB, Prabha V, Malur P, Borges A. Primitive neuroectodermal tumor (PNET) of kidney with level IV inferior venacaval thrombus: A case report. Recent Res Sci Technol 2010;2:38-41.  Back to cited text no. 16
Fergany AF, Dhar N, Budd GT, Skacel M, Garcia JA. Primary extraosseous Ewing sarcoma of the kidney with level III inferior vena cava thrombus. Clin Genitourin Cancer 2009;7:E95-7.  Back to cited text no. 17
Karnes RJ, Gettman MT, Anderson PM, Lager DJ, Blute ML. Primitive neuroectodermal tumor (extraskeletal Ewing's sarcoma) of the kidney with vena caval tumor thrombus. J Urol 2000;164:772.  Back to cited text no. 18
Fontaine C, Schots R, Braeckman J, Goossens A, Soete G, De Grève J. Long-term survival in an adult metastatic renal peripheral primitive neuroectodermal tumor (PPNET) with multimodality treatment including high-dose chemotherapy. Ann Oncol 1997;8:691-4.  Back to cited text no. 19
Huang KH, Shun CT, Huang SY, Yu HJ, Chueh SC, Chen J. Primary primitive neuroectodermal tumor of the urinary tract. J Formos Med Assoc 2006;105:1008-12.  Back to cited text no. 20


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1]

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