Primitive neuroectodermal tumors of the kidney Geetha Narayanan, MD, DM, Varun Rajan, MD, and T. R. Preethi, MD
Ewing’s sarcoma/primitive neuroectodermal tumor (ES ⁄ PNET) rarely occurs as a primary renal tumor. The disease affects young adults and children and has an aggressive course. The clinical presentation and imaging of these tumors are nonspecific, and they often present at an advanced stage. We present the clinical features, imaging, diagnosis, and treatment of 7 cases of renal PNET (4 men, 3 women; median age, 32 years). Common presenting symptoms were flank or abdominal pain and a mass in the abdomen. On imaging, a large heterogenous infiltrating renal mass with areas of calcification, hemorrhage, and necrosis and tumor thrombus can give a clue to the diagnosis of renal PNET. Immunohistochemistry and molecular studies are essential to confirm the diagnosis. The prognosis of renal ES ⁄ PNET is generally poor. Radical nephrectomy combined with chemotherapy and radiotherapy is the standard treatment for renal PNET. An early and accurate diagnosis is crucial for the proper management of these aggressive tumors.
E
wing’s sarcoma/primitive neuroectodermal tumors (ES ⁄ PNET) are a group of small round cell tumors primarily affecting the bone and soft tissues. Very rarely, they can occur as a primary renal tumor (1). The disease commonly affects young adults and children and runs an aggressive course (2). Molecular studies have established that ES and PNET are part of the same tumor family and exhibit similar biologic behavior. Most of the literature on renal PNET consists of isolated case reports. The clinical presentation and imaging of these tumors are nonspecific, and they often present at an advanced stage. We present the clinical features, imaging, diagnosis, and treatment of 7 cases of renal PNET treated in our center. METHODS This is a retrospective analysis of 7 patients diagnosed with PNET of the kidney treated in the Department of Medical Oncology at Regional Cancer Center, Trivandrum, during a 15year period. The case records of the patients were studied with respect to clinical presentation, diagnosis, treatment received, and survival. RESULTS The details of the 7 cases are summarized in Table 1. In our series, the median age was 32 years (range 16–73 years), and Proc (Bayl Univ Med Cent) 2017;30(2):205–208
there were 4 women and 3 men. In all the patients except one, the presenting symptom was abdominal pain and a huge mass in the abdomen. In one case (#1), the renal mass was detected during antenatal checkup when investigating fetal bradycardia. Most of the patients presented at an advanced stage, and 4 out of 7 had metastatic disease at presentation involving the lungs and bone. Computed tomography (CT) imaging details were available in 5 of our cases and showed heterogenous hypodense mass lesions arising from the upper or lower poles of the kidney with areas of hemorrhage and necrosis; 3 cases also had calcifications. Histopathological examination showed a small round blue cell neoplasm in all the cases, and immunohistochemistry, which was available in 5 cases, was positive for CD99. Only 3 of our cases had localized disease, and all underwent radical nephrectomy; however, only 2 received adjuvant chemotherapy with vincristine, doxorubicin, cyclophosphamide/ ifosfamide, etoposide (VDE/IE), and one received adjuvant irradiation to the primary site. Among our 4 cases with metastatic disease, 3 presented following radical nephrectomy, 3 received chemotherapy, and 3 were given palliative irradiation to the metastatic site. Two patients did not receive any systemic treatment after radical nephrectomy, and their follow-up details were not known. Among the 5 patients who received chemotherapy, 4 were alive beyond 1 year, and one is alive in remission at 15 months. The survival of our patient group ranged from 6 months to 18 months. DISCUSSION ES ⁄ PNET of the kidney was first reported by Seemayer and colleagues in 1975 (3) and is exceedingly rare. It usually affects young adults at a median age of 28 years and has a male predominance of 3:1 (4, 5). In our series, the median age was 32 years, and the male:female ratio was 4:3. The common presenting symptoms are flank or abdominal pain, mass in the abdomen, and hematuria (6). Patients are usually asymptomatic until the tumor reaches a large size; the maximum diameter of From the Departments of Medical Oncology (Narayanan, Rajan) and Pathology (Preethi), Regional Cancer Centre, Trivandrum, India. Corresponding author: Geetha Narayanan, MD, DM, Professor and Head, Department of Medical Oncology, Regional Cancer Centre, Trivandrum 695011, Kerala, India (e-mail: [email protected]). 205
Table 1. Summary of clinical presentation and treatment of 7 patients with renal primitive neuroectodermal tumor Clinical Case Age Sex presentation
1
27
2
34
3
17
4
16
5
73
6
35
7
32
CT imaging F Incidental Localized Hypodense enhancing detection durlesion in right kidney, ing antenatal infiltrating the collecting checkup system (Fig. 1) F Abdominal Localized Mass lesion 20 × 13 × lump for 13 cm in right kidney 2 months with calcification, infiltrating right lobe of liver (Fig. 3) F Left hypoMetastatic: Mass lesion 18 × 10 × chondrial orbit (Fig. 4) 13 cm in left kidney with pain, diplopia, multiple hypodensities ptosis and calcifications F Abdominal Metastatic: NA pain and lump; bone presented after nephrectomy M Backache; Metastatic: Heterogeneously enhancing presented lung, bone, hypodense lesion 8.3 × after liver 6.6 cm in lower half of right nephrectomy kidney M Abdominal Localized Heterogeneously enhanclump ing mass lesion 10 × 7 × 10 cm in right kidney with calcification M Flank pain; Metastatic: NA presented after lungs nephrectomy Extent
Immunohistochemistry Surgery CK–, LCA–, Radical SNP–, CG–, CD99 nephrectomy strong+ (Fig. 2) after cesarian section LCA–, PAX5–,Tdt, Radical CD5–, Des–, nephrectomy CD99+, SNP+ at 12 wk of chemo (margin positive) SNP–, CD99+ Renal biopsy only
NA
Chemotherapy Radiation Status VDC/IE No Alive in 17 cycles remission at 15 mo VDC/IE 45 Gy 10 cycles
Died at 15 mo due to sepsis
VDC/IE 20 Gy 13 cycles (orbit)
Progression at 18 mo
Radical VDC nephrectomy 6 cycles
20 Gy (bone)
Progression at 6 mo, BSC
CD99+, Vim+, Radical No CK–, S100–, Des–, nephrectomy CD10–
20 Gy (bone)
2 mo, BSC
CD99+, SNP focally+, CG–
Radical No nephrectomy
No
Lost to follow-up after surgery
CD 99+, NSE+, LCA–
Radical VDC nephrectomy 9 cycles
No
Progression at 14 mo
BSC indicates best supportive care; CG, chromogranin; CK, cytokeratin; Des, Desmin; IE, ifosfamide, etoposide; LCA, leukocyte common antigen; NSE, neuron-specific enolase; SNP, synaptophysin; Tdt, terminal deoxynucleotidyl transferase; VDC, vincristine, doxorubicin, cyclophosphamide; Vim, vimentin.
a
c
b
Figure 1. (a) Plain CT scan of the abdomen, axial view, showing a large isodense lesion involving the right kidney causing contour distortion and enlargement. (b) Contrast-enhanced CT image showing moderately enhancing nonhomogeneous mass with involvement of the collecting system and infiltration of the right psoas muscle. (c) Plain CT coronal section showing enlargement of the right kidney with loss of fat plane with right lobe of liver. 206
such tumors is often 10 cm (7, 8). Systemic symptoms such as weight loss and fever may also occur (9). Our patients presented similarly, except in one patient in whom the renal mass was detected during antenatal checkup. Most of the patients present at an advanced stage with distant metastasis, which is in concordance with the aggressive behavior of this tumor (4, 10). Common sites of metastasis include the lung, liver, and bone (6). In our series, 4 out of 7 had metastatic disease at presentation involving the lungs and bone. The imaging characteristics of renal PNET are often nonspecific and overlap with those of other renal tumors, such as renal cell carcinoma, Wilms tumor, neuroblastoma, lymphoma, and desmoplastic small round cell tumor (11). Renal PNETs appear hypoechoic, isoechoic, and ⁄or hyperechoic to the adjacent renal parenchyma on ultrasound and show increased vascularity on Doppler imaging. CT scan shows a large heterogenous mass with areas of hemorrhage or necrosis (12). On magnetic resonance imaging (MRI), the tumor appears as a lobulated isointense and ⁄or hypointense mass on T1-weighted images and as a heterogeneous to hyperintense mass on T2-weighted images, with heterogenous contrast enhancement (6, 12). MRI and CT also help to evaluate renal vein and inferior vena caval
Baylor University Medical Center Proceedings
Volume 30, Number 2
is also positive for different neural biomarkers such as S-100, Leu 7, and NSE (13). The immunohistochemistry findings are further supported by the identification of a characteristic EWSR1⁄FLI1 fusion product that results from a t(11;22) (q24⁄q22;q12) translocation. This translocation is identified in 90% of cases and unequivocally confirms the diagnosis (7, 14). Among our cases, IHC details were available in 5 patients, and all were positive for CD99. Renal PNET appears to be a unique clinical entity that behaves more aggressively than PNET arisFigure 2. (a) Hematoxylin and eosin stain (40×) showing the neoplasm composed of large nests of cells with a moderate amount of cytoplasm, moderately pleomorphic nuclei with granular chromatin, and areas of geographic necrosis, with ing at other sites. As the tumor is highly aggressive, it is often diagthin vascular channels in between. Scattered mitosis was seen. (b) MIC-2 (CD99) shows strong membrane positivity. nosed in an advanced stage when it has already involved perinephric fat, hilar lymph nodes, renal veins, and the inferior vena cava. involvement. Technetium-99m scintigraphy is useful for the In more advanced stages, the tumor involves the liver, spleen, detection of bone metastases (6). CT imaging details were availperitoneum, and lungs. The prognosis for renal ES ⁄ PNET is able in 5 of our cases and showed mass lesions arising from the upper or lower poles of the kidney, 3 with calcifications. generally poor, with a 5-year disease-free survival of 45% to Diagnosis of renal PNET is challenging. Although radio55% in localized cases, whereas cases with an advanced stage at logical features may be suggestive, biopsy with immunohistopresentation have a median relapse-free survival of only 2 years chemistry is required to confirm the diagnosis. Renal PNET is (9, 13, 15). characterized by small uniform round cells with dark nuclei, The treatment for renal ES ⁄ PNET is similar to that for ill-defined cytoplasmic borders, and poorly formed rosette-like ES/PNET elsewhere and includes surgery, chemotherapy, structures (9). The histopathologic features overlap with other and radiation (6, 10). Surgical options include partial or total small round blue cell tumors like neuroblastoma, desmoplastic nephrectomy with cavotomy in cases of renal vein involvement small round cell tumor, and lymphoma. Immunohistochem(6, 14). The diagnosis of renal ES ⁄ PNET is often made postistry and molecular studies play a crucial role in differentiatoperatively and hence chemotherapy is generally given as an ing these tumors. PNET shows strong positivity for MIC-2 adjuvant. The recommended chemotherapy regimen is vingene product and CD-99 over the membrane of tumor cells, cristine, doxorubicin, and cyclophosphamide alternating with which is seen in more than 90% of renal PNET cases (7). It ifosfamide and etoposide given for a period of 1 year (16). The role of radiotherapy is not clear, but it may be given in locally adb a vanced disease and in those with positive margins. Despite aggressive therapy, the overall cure rate of renal PNET is only 20% (17). Among the 7 cases reported here, 6 underwent radical nephrectomy, 5 received chemotherapy, and 4 received radiation therapy. Four patients were alive beyond 1 year, and one is alive in remission at 15 months. The survival of our patient group ranged from 6 months to 18 months. Since the overall prognosis of this tumor is poor, an early and accurate diagnosis is crucial for the Figure 3. Contrast-enhanced CT of the abdomen showing a large irregular heterogeneously enhancing mass lesion proper management of these aggressive tumors. arising from the upper pole of the right kidney, with multiple specks of calcification within. a
April 2017
b
Primitive neuroectodermal tumors of the kidney
207
5.
6. 7.
8.
9.
10.
11.
12.
13.
Figure 4. Technetium-99m scintigraphy bone scan showing increased uptake over the lateral margin of the left orbital ridge. 1.
2.
3. 4.
208
Pomara G, Cappello F, Cuttano MG, Rappa F, Morelli G, Mansini P, Selli C. Primitive neuroectodermal tumor (PNET) of the kidney: a case report. BMC Cancer 2004;4(1):3. Jimenez RE, Folpe AL, Lapham RL, Ro JY, O’Shea PA, Weiss SW, Amin MB. Primary Ewing’s sarcoma/primitive neuroectodermal tumor of the kidney: a clinicopathologic and immunohistochemical analysis of 11 cases. Am J Surg Pathol 2002;26(3):320–327. Seemayer TA, Thelmo WL, Bolande RP, Wiglesworth FW. Peripheral neuroectodermal tumors. Perspect Pediatr Pathol 1975;2:151–172. Mohsin R, Hashmi A, Mubarak M, Sultan G, Shehzad A, Qayum A, Anwer Naqvi SA, Hassan Rizvi SA. Primitive neuroectodermal tumor/Ewing’s
14.
15.
16.
17.
sarcoma in adult uro-oncology: a case series from a developing country. Urol Ann 2011;3(2):103–107. Lee H, Cho JY, Kim SH, Jung DC, Kim JK, Choi HJ. Imaging findings of primitive neuroectodermal tumors of the kidney. J Comput Assist Tomogr 2009;33(6):882–886. Hari S, Jain TP, Thulkar S, Bakhshi S. Imaging features of peripheral primitive neuroectodermal tumours. Br J Radiol 2008;81(972):975–983. Wu YJ, Zhu YC, Chen H, Huang Y, Wei Q, Chen HJ, Xie X, Li X, Zhou Q, Yang YR, Zeng H. Primitive neuroectodermal tumor of the kidney with inferior vena cava tumor thrombus during pregnancy response to sorafenib. Chin Med J (Engl) 2010;123(15):2155–2158. Ohgaki K, Horiuchi K, Mizutani S, Sato M, Kondo Y. Primary Ewing’s sarcoma/primitive neuroectodermal tumor of the kidney that responded to low-dose chemotherapy with ifosfamide, etoposide, and doxorubicin. Int J Clin Oncol 2010;15(2):210–214. Parham DM, Roloson GJ, Feely M, Green DM, Bridge JA, Beckwith JB. Primary malignant neuroepithelial tumors of the kidney: a clinicopathologic analysis of 146 adult and pediatric cases from the National Wilms’ Tumor Study Group Pathology Center. Am J Surg Pathol 2001;25(2):133–146. Ellinger J, Bastian PJ, Hauser S, Biermann K, Müller SC. Primitive neuroectodermal tumor: rare, highly aggressive differential diagnosis in urologic malignancies. Urology 2006;68(2):257–262. Lalwani N, Prasad SR, Vikram R, Katabathina V, Shanbhogue A, Restrepo C. Pediatric and adult primary sarcomas of the kidney: a crosssectional imaging review. Acta Radiol 2011;52(4):448–457. Tappouni R, El-Kady R, Raman J, Then M, Sarwani N. Renal neuroectodermal tumour presenting with hematuria. J Radiol Case Rep 2010;4(7):12–20. Habermann H, Benesch M, Schips L, Pummera K, Ratschekc M, Uggowitzerd MM, Urbanb C, Hubmera G. Findings and clinical course of a localized primitive peripheral neuroectodermal tumor of the kidney. Urol Int 2003;71(3):319–321. 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(3):E95–E97. Casella R, Moch H, Rochiltz C, Meier V, Seifert B, Mihatsch MJ, Gasser TC. Metastatic primitive neuroectodermal tumor of the kidney in adults. Eur Urol 2001;39(5):613–617. Grier HE, Krailo MD, Tarbell NJ, Link MP, Fryer CJ, Pritchard DJ, Gebhardt MC, Dickman PS, Perlman EJ, Meyers PA, Donaldson SS, Moore S, Rausen AR, Vietti TJ, Miser JS. Addition of ifosfamide and etoposide to standard chemotherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med 2003;348(8):694–701. Angel JR, Alfred A, Sakhuja A, Sells RE, Zechlinski JJ. Ewing’s sarcoma of the kidney. Int J Clin Oncol 2010;15(3):314–318.
Baylor University Medical Center Proceedings
Volume 30, Number 2
Ewing’s sarcoma/primitive neuroectodermal tumor (ES ⁄ PNET) rarely occurs as a primary renal tumor. The disease affects young adults and children and has an aggressive course. The clinical presentation and imaging of these tumors are nonspecific, and they often present at an advanced stage. We present the clinical features, imaging, diagnosis, and treatment of 7 cases of renal PNET (4 men, 3 women; median age, 32 years). Common presenting symptoms were flank or abdominal pain and a mass in the abdomen. On imaging, a large heterogenous infiltrating renal mass with areas of calcification, hemorrhage, and necrosis and tumor thrombus can give a clue to the diagnosis of renal PNET. Immunohistochemistry and molecular studies are essential to confirm the diagnosis. The prognosis of renal ES ⁄ PNET is generally poor. Radical nephrectomy combined with chemotherapy and radiotherapy is the standard treatment for renal PNET. An early and accurate diagnosis is crucial for the proper management of these aggressive tumors.
E
wing’s sarcoma/primitive neuroectodermal tumors (ES ⁄ PNET) are a group of small round cell tumors primarily affecting the bone and soft tissues. Very rarely, they can occur as a primary renal tumor (1). The disease commonly affects young adults and children and runs an aggressive course (2). Molecular studies have established that ES and PNET are part of the same tumor family and exhibit similar biologic behavior. Most of the literature on renal PNET consists of isolated case reports. The clinical presentation and imaging of these tumors are nonspecific, and they often present at an advanced stage. We present the clinical features, imaging, diagnosis, and treatment of 7 cases of renal PNET treated in our center. METHODS This is a retrospective analysis of 7 patients diagnosed with PNET of the kidney treated in the Department of Medical Oncology at Regional Cancer Center, Trivandrum, during a 15year period. The case records of the patients were studied with respect to clinical presentation, diagnosis, treatment received, and survival. RESULTS The details of the 7 cases are summarized in Table 1. In our series, the median age was 32 years (range 16–73 years), and Proc (Bayl Univ Med Cent) 2017;30(2):205–208
there were 4 women and 3 men. In all the patients except one, the presenting symptom was abdominal pain and a huge mass in the abdomen. In one case (#1), the renal mass was detected during antenatal checkup when investigating fetal bradycardia. Most of the patients presented at an advanced stage, and 4 out of 7 had metastatic disease at presentation involving the lungs and bone. Computed tomography (CT) imaging details were available in 5 of our cases and showed heterogenous hypodense mass lesions arising from the upper or lower poles of the kidney with areas of hemorrhage and necrosis; 3 cases also had calcifications. Histopathological examination showed a small round blue cell neoplasm in all the cases, and immunohistochemistry, which was available in 5 cases, was positive for CD99. Only 3 of our cases had localized disease, and all underwent radical nephrectomy; however, only 2 received adjuvant chemotherapy with vincristine, doxorubicin, cyclophosphamide/ ifosfamide, etoposide (VDE/IE), and one received adjuvant irradiation to the primary site. Among our 4 cases with metastatic disease, 3 presented following radical nephrectomy, 3 received chemotherapy, and 3 were given palliative irradiation to the metastatic site. Two patients did not receive any systemic treatment after radical nephrectomy, and their follow-up details were not known. Among the 5 patients who received chemotherapy, 4 were alive beyond 1 year, and one is alive in remission at 15 months. The survival of our patient group ranged from 6 months to 18 months. DISCUSSION ES ⁄ PNET of the kidney was first reported by Seemayer and colleagues in 1975 (3) and is exceedingly rare. It usually affects young adults at a median age of 28 years and has a male predominance of 3:1 (4, 5). In our series, the median age was 32 years, and the male:female ratio was 4:3. The common presenting symptoms are flank or abdominal pain, mass in the abdomen, and hematuria (6). Patients are usually asymptomatic until the tumor reaches a large size; the maximum diameter of From the Departments of Medical Oncology (Narayanan, Rajan) and Pathology (Preethi), Regional Cancer Centre, Trivandrum, India. Corresponding author: Geetha Narayanan, MD, DM, Professor and Head, Department of Medical Oncology, Regional Cancer Centre, Trivandrum 695011, Kerala, India (e-mail: [email protected]). 205
Table 1. Summary of clinical presentation and treatment of 7 patients with renal primitive neuroectodermal tumor Clinical Case Age Sex presentation
1
27
2
34
3
17
4
16
5
73
6
35
7
32
CT imaging F Incidental Localized Hypodense enhancing detection durlesion in right kidney, ing antenatal infiltrating the collecting checkup system (Fig. 1) F Abdominal Localized Mass lesion 20 × 13 × lump for 13 cm in right kidney 2 months with calcification, infiltrating right lobe of liver (Fig. 3) F Left hypoMetastatic: Mass lesion 18 × 10 × chondrial orbit (Fig. 4) 13 cm in left kidney with pain, diplopia, multiple hypodensities ptosis and calcifications F Abdominal Metastatic: NA pain and lump; bone presented after nephrectomy M Backache; Metastatic: Heterogeneously enhancing presented lung, bone, hypodense lesion 8.3 × after liver 6.6 cm in lower half of right nephrectomy kidney M Abdominal Localized Heterogeneously enhanclump ing mass lesion 10 × 7 × 10 cm in right kidney with calcification M Flank pain; Metastatic: NA presented after lungs nephrectomy Extent
Immunohistochemistry Surgery CK–, LCA–, Radical SNP–, CG–, CD99 nephrectomy strong+ (Fig. 2) after cesarian section LCA–, PAX5–,Tdt, Radical CD5–, Des–, nephrectomy CD99+, SNP+ at 12 wk of chemo (margin positive) SNP–, CD99+ Renal biopsy only
NA
Chemotherapy Radiation Status VDC/IE No Alive in 17 cycles remission at 15 mo VDC/IE 45 Gy 10 cycles
Died at 15 mo due to sepsis
VDC/IE 20 Gy 13 cycles (orbit)
Progression at 18 mo
Radical VDC nephrectomy 6 cycles
20 Gy (bone)
Progression at 6 mo, BSC
CD99+, Vim+, Radical No CK–, S100–, Des–, nephrectomy CD10–
20 Gy (bone)
2 mo, BSC
CD99+, SNP focally+, CG–
Radical No nephrectomy
No
Lost to follow-up after surgery
CD 99+, NSE+, LCA–
Radical VDC nephrectomy 9 cycles
No
Progression at 14 mo
BSC indicates best supportive care; CG, chromogranin; CK, cytokeratin; Des, Desmin; IE, ifosfamide, etoposide; LCA, leukocyte common antigen; NSE, neuron-specific enolase; SNP, synaptophysin; Tdt, terminal deoxynucleotidyl transferase; VDC, vincristine, doxorubicin, cyclophosphamide; Vim, vimentin.
a
c
b
Figure 1. (a) Plain CT scan of the abdomen, axial view, showing a large isodense lesion involving the right kidney causing contour distortion and enlargement. (b) Contrast-enhanced CT image showing moderately enhancing nonhomogeneous mass with involvement of the collecting system and infiltration of the right psoas muscle. (c) Plain CT coronal section showing enlargement of the right kidney with loss of fat plane with right lobe of liver. 206
such tumors is often 10 cm (7, 8). Systemic symptoms such as weight loss and fever may also occur (9). Our patients presented similarly, except in one patient in whom the renal mass was detected during antenatal checkup. Most of the patients present at an advanced stage with distant metastasis, which is in concordance with the aggressive behavior of this tumor (4, 10). Common sites of metastasis include the lung, liver, and bone (6). In our series, 4 out of 7 had metastatic disease at presentation involving the lungs and bone. The imaging characteristics of renal PNET are often nonspecific and overlap with those of other renal tumors, such as renal cell carcinoma, Wilms tumor, neuroblastoma, lymphoma, and desmoplastic small round cell tumor (11). Renal PNETs appear hypoechoic, isoechoic, and ⁄or hyperechoic to the adjacent renal parenchyma on ultrasound and show increased vascularity on Doppler imaging. CT scan shows a large heterogenous mass with areas of hemorrhage or necrosis (12). On magnetic resonance imaging (MRI), the tumor appears as a lobulated isointense and ⁄or hypointense mass on T1-weighted images and as a heterogeneous to hyperintense mass on T2-weighted images, with heterogenous contrast enhancement (6, 12). MRI and CT also help to evaluate renal vein and inferior vena caval
Baylor University Medical Center Proceedings
Volume 30, Number 2
is also positive for different neural biomarkers such as S-100, Leu 7, and NSE (13). The immunohistochemistry findings are further supported by the identification of a characteristic EWSR1⁄FLI1 fusion product that results from a t(11;22) (q24⁄q22;q12) translocation. This translocation is identified in 90% of cases and unequivocally confirms the diagnosis (7, 14). Among our cases, IHC details were available in 5 patients, and all were positive for CD99. Renal PNET appears to be a unique clinical entity that behaves more aggressively than PNET arisFigure 2. (a) Hematoxylin and eosin stain (40×) showing the neoplasm composed of large nests of cells with a moderate amount of cytoplasm, moderately pleomorphic nuclei with granular chromatin, and areas of geographic necrosis, with ing at other sites. As the tumor is highly aggressive, it is often diagthin vascular channels in between. Scattered mitosis was seen. (b) MIC-2 (CD99) shows strong membrane positivity. nosed in an advanced stage when it has already involved perinephric fat, hilar lymph nodes, renal veins, and the inferior vena cava. involvement. Technetium-99m scintigraphy is useful for the In more advanced stages, the tumor involves the liver, spleen, detection of bone metastases (6). CT imaging details were availperitoneum, and lungs. The prognosis for renal ES ⁄ PNET is able in 5 of our cases and showed mass lesions arising from the upper or lower poles of the kidney, 3 with calcifications. generally poor, with a 5-year disease-free survival of 45% to Diagnosis of renal PNET is challenging. Although radio55% in localized cases, whereas cases with an advanced stage at logical features may be suggestive, biopsy with immunohistopresentation have a median relapse-free survival of only 2 years chemistry is required to confirm the diagnosis. Renal PNET is (9, 13, 15). characterized by small uniform round cells with dark nuclei, The treatment for renal ES ⁄ PNET is similar to that for ill-defined cytoplasmic borders, and poorly formed rosette-like ES/PNET elsewhere and includes surgery, chemotherapy, structures (9). The histopathologic features overlap with other and radiation (6, 10). Surgical options include partial or total small round blue cell tumors like neuroblastoma, desmoplastic nephrectomy with cavotomy in cases of renal vein involvement small round cell tumor, and lymphoma. Immunohistochem(6, 14). The diagnosis of renal ES ⁄ PNET is often made postistry and molecular studies play a crucial role in differentiatoperatively and hence chemotherapy is generally given as an ing these tumors. PNET shows strong positivity for MIC-2 adjuvant. The recommended chemotherapy regimen is vingene product and CD-99 over the membrane of tumor cells, cristine, doxorubicin, and cyclophosphamide alternating with which is seen in more than 90% of renal PNET cases (7). It ifosfamide and etoposide given for a period of 1 year (16). The role of radiotherapy is not clear, but it may be given in locally adb a vanced disease and in those with positive margins. Despite aggressive therapy, the overall cure rate of renal PNET is only 20% (17). Among the 7 cases reported here, 6 underwent radical nephrectomy, 5 received chemotherapy, and 4 received radiation therapy. Four patients were alive beyond 1 year, and one is alive in remission at 15 months. The survival of our patient group ranged from 6 months to 18 months. Since the overall prognosis of this tumor is poor, an early and accurate diagnosis is crucial for the Figure 3. Contrast-enhanced CT of the abdomen showing a large irregular heterogeneously enhancing mass lesion proper management of these aggressive tumors. arising from the upper pole of the right kidney, with multiple specks of calcification within. a
April 2017
b
Primitive neuroectodermal tumors of the kidney
207
5.
6. 7.
8.
9.
10.
11.
12.
13.
Figure 4. Technetium-99m scintigraphy bone scan showing increased uptake over the lateral margin of the left orbital ridge. 1.
2.
3. 4.
208
Pomara G, Cappello F, Cuttano MG, Rappa F, Morelli G, Mansini P, Selli C. Primitive neuroectodermal tumor (PNET) of the kidney: a case report. BMC Cancer 2004;4(1):3. Jimenez RE, Folpe AL, Lapham RL, Ro JY, O’Shea PA, Weiss SW, Amin MB. Primary Ewing’s sarcoma/primitive neuroectodermal tumor of the kidney: a clinicopathologic and immunohistochemical analysis of 11 cases. Am J Surg Pathol 2002;26(3):320–327. Seemayer TA, Thelmo WL, Bolande RP, Wiglesworth FW. Peripheral neuroectodermal tumors. Perspect Pediatr Pathol 1975;2:151–172. Mohsin R, Hashmi A, Mubarak M, Sultan G, Shehzad A, Qayum A, Anwer Naqvi SA, Hassan Rizvi SA. Primitive neuroectodermal tumor/Ewing’s
14.
15.
16.
17.
sarcoma in adult uro-oncology: a case series from a developing country. Urol Ann 2011;3(2):103–107. Lee H, Cho JY, Kim SH, Jung DC, Kim JK, Choi HJ. Imaging findings of primitive neuroectodermal tumors of the kidney. J Comput Assist Tomogr 2009;33(6):882–886. Hari S, Jain TP, Thulkar S, Bakhshi S. Imaging features of peripheral primitive neuroectodermal tumours. Br J Radiol 2008;81(972):975–983. Wu YJ, Zhu YC, Chen H, Huang Y, Wei Q, Chen HJ, Xie X, Li X, Zhou Q, Yang YR, Zeng H. Primitive neuroectodermal tumor of the kidney with inferior vena cava tumor thrombus during pregnancy response to sorafenib. Chin Med J (Engl) 2010;123(15):2155–2158. Ohgaki K, Horiuchi K, Mizutani S, Sato M, Kondo Y. Primary Ewing’s sarcoma/primitive neuroectodermal tumor of the kidney that responded to low-dose chemotherapy with ifosfamide, etoposide, and doxorubicin. Int J Clin Oncol 2010;15(2):210–214. Parham DM, Roloson GJ, Feely M, Green DM, Bridge JA, Beckwith JB. Primary malignant neuroepithelial tumors of the kidney: a clinicopathologic analysis of 146 adult and pediatric cases from the National Wilms’ Tumor Study Group Pathology Center. Am J Surg Pathol 2001;25(2):133–146. Ellinger J, Bastian PJ, Hauser S, Biermann K, Müller SC. Primitive neuroectodermal tumor: rare, highly aggressive differential diagnosis in urologic malignancies. Urology 2006;68(2):257–262. Lalwani N, Prasad SR, Vikram R, Katabathina V, Shanbhogue A, Restrepo C. Pediatric and adult primary sarcomas of the kidney: a crosssectional imaging review. Acta Radiol 2011;52(4):448–457. Tappouni R, El-Kady R, Raman J, Then M, Sarwani N. Renal neuroectodermal tumour presenting with hematuria. J Radiol Case Rep 2010;4(7):12–20. Habermann H, Benesch M, Schips L, Pummera K, Ratschekc M, Uggowitzerd MM, Urbanb C, Hubmera G. Findings and clinical course of a localized primitive peripheral neuroectodermal tumor of the kidney. Urol Int 2003;71(3):319–321. 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(3):E95–E97. Casella R, Moch H, Rochiltz C, Meier V, Seifert B, Mihatsch MJ, Gasser TC. Metastatic primitive neuroectodermal tumor of the kidney in adults. Eur Urol 2001;39(5):613–617. Grier HE, Krailo MD, Tarbell NJ, Link MP, Fryer CJ, Pritchard DJ, Gebhardt MC, Dickman PS, Perlman EJ, Meyers PA, Donaldson SS, Moore S, Rausen AR, Vietti TJ, Miser JS. Addition of ifosfamide and etoposide to standard chemotherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med 2003;348(8):694–701. Angel JR, Alfred A, Sakhuja A, Sells RE, Zechlinski JJ. Ewing’s sarcoma of the kidney. Int J Clin Oncol 2010;15(3):314–318.
Baylor University Medical Center Proceedings
Volume 30, Number 2
