DOI: 10.5301/urologia.5000033
Urologia 2014 ; 81 ( 1): 57-59
CASE REPORT
Primary large cell neuroendocrine carcinoma of the renal pelvis: a case report Carlotta Palumbo 1, Michele Talso 1, Paolo Guido Dell’Orto 1, Gabriele Cozzi 1, Elisa De Lorenzis 1, Andrea Conti 1, Marco Maggioni 2, Bernardo Maria Cesare Rocco 1, Augusto Maggioni 1, Francesco Rocco 1 Department of Urology, University of Milan, IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milan - Italy Department of Anatomopathology, University of Milan, IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milan - Italy
1 2
We report a case of primary large cell neuroendocrine carcinoma of the renal pelvis, diagnosed in a 79-year-old man. The abdominal computed tomography showed a solid, vegetant lesion in the left renal pelvis, conditioning marked hydronephrosis. The patient underwent radical nephroureterectomy. The histological examination showed a large cell neuroendocrine carcinoma associated with a high-grade urothelial carcinoma, with local invasion (pT3). Large cell renal neuroendocrine carcinomas are rare tumors with an aggressive course and a bad prognosis. At present, only five cases were reported in literature. Key words: Large cell neuroendocrine carcinoma, Urothelial cell carcinoma, Kidney, Nephroureterectomy Parole chiave: Carcinoma neuroendocrino a grandi cellule, Carcinoma a cellule uroteliali, Rene, Nefroureterectomia Accepted: July 29, 2013
Introduction Neuroendocrine (NE) tumors represent a heterogeneous group of neoplasms originating from neuroendocrine cells. In the urinary tract, NE tumors are distinguished into carcinoid tumors, small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas. Renal NE tumors are very uncommon, because neuroendocrine cells are not present in normal renal parenchyma, pelvis and ureter (1). We report a case of primary large cell neuroendocrine carcinoma of the renal pelvis, diagnosed in a 79-year-old male.
Case report An asymptomatic 79-year-old man presented to our hospital after an abdominal ultrasonography (US), performed because of impaired renal function (serum creatinine
1.81 mg/dL). US showed a volumetric increasing of the left kidney (~13 cm) due to marked hydronephrosis with a ~6 cm pelvic diameter and calyceal dilatation. A vegetant hyperechogenic lesion was detected at the level of the left pyeloureteral junction. Bladder images were normal. Subsequently, the patient performed a contrast-enhanced abdominal computed tomography (CT) showing an evident hydronephrosis of the left kidney with reduction of the parenchymal thickness and, in the renal pelvis, just before the pyeloureteral junction, a solid, broad-based, contrast-enhanced exophytic lesion with the largest diameter of 3.5 cm, suggestive of neoplasm. The bladder resulted to be normal and no retroperitoneal lymphoadenomegalies were documented. At the flexible cystoscopy, no bladder lesions were detected. The patient’s past medical history highlighted a radical retropubic prostatectomy with lymphadenectomy 15 years before and an open left hemicolectomy 1 year before.
© 2013 Wichtig Editore - ISSN 0391-5603
57
Neuroendocrine carcinoma of renal pelvis
Fig. 1 - The biphasic nature of the tumor was evident at low magnification, with a more densely cellular component, with organoid pattern (right), and a less cellular component, with more stroma (left). H&E, 100×.
The patient underwent left nephroureterectomy with excision of the bladder cuff with xifopubic incision and retroperitoneal approach. The left adrenal gland was preserved. No adenopathies were detected in the para-aortic region, and a para-aortic lymphoadenectomy was not performed because of tissue fibrosis. After surgery, the patient was admitted to post-operative intensive care unit, where he received blood and fresh frozen plasma units. On the 7th day the patient was discharged in good clinical conditions, after cystography and catheter removal. The gross examination of the surgical specimen showed an exophytic whitish tumor in the renal pelvis, 3 cm in the major diameter, macroscopically, infiltrating the renal parenchyma and the adipose peri-hilar tissue. The histological examination demonstrated a high-grade neuroendocrine carcinoma (Fig. 1 and Fig. 2) with vascular invasion and elevated Ki-67 proliferative index (80%), associated with a high-grade urothelial carcinoma (according to WHO, 2004). Infiltration of the renal parenchyma and fat tissue was histologically confirmed (TNM stage pT3). The tumor was associated with interstitial peritumoral nephritis and nephrogenic metaplasia of the superior calyces. Ureteral and vascular margins were free from neoplasia. The neuroendocrine nature of the tumor was confirmed by immunocytochemistry, with positive staining to Chromogranin A, Synaptophysin and CD56; high molecular weight keratins (34-E12) was expressed in the urothelial but not in 58
Fig. 2 - At higher magnification, the neuroendocrine cells in the lower part of the picture demonstrated highly basophylic nuclei with apoptotic bodies and scanty cytoplasm, while atypical urothelial cells in the upper part are characterized by bigger nucleolated nuclei and more abundant eosinophilic cytoplasm. H&E, 400×.
Fig. 3 - Immunocytochemical panel showing expression of high molecular weight keratins 34-E12 in the urothelial but not in the neuroendocrine cells (A), while neuroendocrine markers CD56 (B), Chromogranin A (C) and Synaptophysin (D) are positive only in the neuroendocrine component of the tumor. 200×.
the neuroendocrine cells; conversely, urothelial cells were negative to neuroendocrine markers (Fig. 3). Following nephroureterectomy, the patient was referred to our oncological department. Due to his cardiac comorbidities and his poor prognosis, the patient did not undergo chemotherapy. He died 4 months after surgery because of the disease.
© 2013 Wichtig Editore - ISSN 0391-5603
Palumbo et al
Discussion Neuroendocrine tumors are malignant tumors arising from enterochromaffin or amine precursor uptake and decarboxylation (APUD) cells. Neuroendocrine tumors most commonly involve the gastrointestinal tract, which account for approximately 70% of all cases, and the respiratory system. This kind of neoplasms is rarely observed in the urinary tract (2). Primary renal neuroendocrine tumors are extremely rare lesions and their origin is still uncertain because neuroendocrine cells are not present in the normal renal parenchyma, pelvis and ureter; on the other hand, these cells are present in the bladder and prostate. The most popular hypothesis about the origin of primary renal neuroendocrine tumors is that primary renal neuroendocrine tumors arise from totipotential primitive stem cells capable of neuroendocrine, mesenchymal and epithelial differentiation (3). Neuroendocrine tumors of the kidney are subdivided into epithelial and neural types (4). Neural types of renal NE tumors include primitive neuroectodermal tumor, neuroblastoma and paraganglioma and usually arise in the renal parenchyma. Epithelial neoplasms usually arise in the renal pelvis, and are divided in carcinoid tumor, small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma. They can be associated with other types of tumors such as transitional cell carcinoma, adenocarcinoma and squamous cell carcinoma (5). Actually, about 90 cases were reported in literature and, to the best of our knowledge, only 5 cases of large cell renal NE tumor have been reported to date. Most patients presented in the fourth to seventh decade with abdominal, back or flank pain, accompanied by hematuria and fever, even if about 25-30% of renal neuroendocrine tumors are incidentally detected. Symptoms of the
REFERENCES 1.
2. 3.
carcinoid syndrome are uncommon and they are seen in less than 10% of all cases (6). Large cell renal NE tumors seem to have an aggressive course and a worse prognosis. At the diagnosis, the patients were asymptomatic or had aspecific symptoms, despite the tumor had a local invasion and presented an advanced pathological stage at histological examination. The patients died within few months after surgery, despite radical surgery.
Conclusions Large cell renal neuroendocrine carcinoma is a highly aggressive tumor and patients often present with locally advanced disease. In conclusion, we described a case of large cell neuroendocrine carcinoma of the renal pelvis. There is still a small number of studies reported in literature; therefore, it is difficult to assess the biological behavior and the potential prognostic factors of these tumors. Disclaimers Informed consent: The manuscript does not report the results of an experimental investigation on human subjects. Financial support: No financial support (grants and funds) received in support of the study. Conflict of interest: None. Corresponding Author: Carlotta Palumbo, MD Clinica Urologica I, Università degli Studi di Milan IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano Via della Commenda, 15 20122 Milan, Italy [email protected]
4.
Kloppel G. Tumour biology and histopathology of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. 2007;21:15-31. Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med. 1999;340:858-68. Lane BR, Chery F, Jour G, et al. Renal neuroendocrine tumours: a clinicopathological study. BJU Int. 2007;100:1030-1035.
5.
6.
Dundr P, Pešl M, Povýšil C, et al. Primary large cell neuroendocrine carcinoma of the kidney. Pathol. Oncol. Res. 2010; 16:139-142. Mazzucchelli R, Morichetti D, Lopez-Beltran A, et al. Neuroendocrine tumours of the urinary system and male genital organs: clinical significance. BJU Int. 2009;103(11):1464-70. Murali R, Kneale K, Lalak N, Delprado W. Carcinoid tumors of the urinary tract and prostate. Arch Pathol Lab Med. 2006;130:1693-706.
© 2013 Wichtig Editore - ISSN 0391-5603
59
Copyright of Urologia is the property of Wichtig Editore and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Urologia 2014 ; 81 ( 1): 57-59
CASE REPORT
Primary large cell neuroendocrine carcinoma of the renal pelvis: a case report Carlotta Palumbo 1, Michele Talso 1, Paolo Guido Dell’Orto 1, Gabriele Cozzi 1, Elisa De Lorenzis 1, Andrea Conti 1, Marco Maggioni 2, Bernardo Maria Cesare Rocco 1, Augusto Maggioni 1, Francesco Rocco 1 Department of Urology, University of Milan, IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milan - Italy Department of Anatomopathology, University of Milan, IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Milan - Italy
1 2
We report a case of primary large cell neuroendocrine carcinoma of the renal pelvis, diagnosed in a 79-year-old man. The abdominal computed tomography showed a solid, vegetant lesion in the left renal pelvis, conditioning marked hydronephrosis. The patient underwent radical nephroureterectomy. The histological examination showed a large cell neuroendocrine carcinoma associated with a high-grade urothelial carcinoma, with local invasion (pT3). Large cell renal neuroendocrine carcinomas are rare tumors with an aggressive course and a bad prognosis. At present, only five cases were reported in literature. Key words: Large cell neuroendocrine carcinoma, Urothelial cell carcinoma, Kidney, Nephroureterectomy Parole chiave: Carcinoma neuroendocrino a grandi cellule, Carcinoma a cellule uroteliali, Rene, Nefroureterectomia Accepted: July 29, 2013
Introduction Neuroendocrine (NE) tumors represent a heterogeneous group of neoplasms originating from neuroendocrine cells. In the urinary tract, NE tumors are distinguished into carcinoid tumors, small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas. Renal NE tumors are very uncommon, because neuroendocrine cells are not present in normal renal parenchyma, pelvis and ureter (1). We report a case of primary large cell neuroendocrine carcinoma of the renal pelvis, diagnosed in a 79-year-old male.
Case report An asymptomatic 79-year-old man presented to our hospital after an abdominal ultrasonography (US), performed because of impaired renal function (serum creatinine
1.81 mg/dL). US showed a volumetric increasing of the left kidney (~13 cm) due to marked hydronephrosis with a ~6 cm pelvic diameter and calyceal dilatation. A vegetant hyperechogenic lesion was detected at the level of the left pyeloureteral junction. Bladder images were normal. Subsequently, the patient performed a contrast-enhanced abdominal computed tomography (CT) showing an evident hydronephrosis of the left kidney with reduction of the parenchymal thickness and, in the renal pelvis, just before the pyeloureteral junction, a solid, broad-based, contrast-enhanced exophytic lesion with the largest diameter of 3.5 cm, suggestive of neoplasm. The bladder resulted to be normal and no retroperitoneal lymphoadenomegalies were documented. At the flexible cystoscopy, no bladder lesions were detected. The patient’s past medical history highlighted a radical retropubic prostatectomy with lymphadenectomy 15 years before and an open left hemicolectomy 1 year before.
© 2013 Wichtig Editore - ISSN 0391-5603
57
Neuroendocrine carcinoma of renal pelvis
Fig. 1 - The biphasic nature of the tumor was evident at low magnification, with a more densely cellular component, with organoid pattern (right), and a less cellular component, with more stroma (left). H&E, 100×.
The patient underwent left nephroureterectomy with excision of the bladder cuff with xifopubic incision and retroperitoneal approach. The left adrenal gland was preserved. No adenopathies were detected in the para-aortic region, and a para-aortic lymphoadenectomy was not performed because of tissue fibrosis. After surgery, the patient was admitted to post-operative intensive care unit, where he received blood and fresh frozen plasma units. On the 7th day the patient was discharged in good clinical conditions, after cystography and catheter removal. The gross examination of the surgical specimen showed an exophytic whitish tumor in the renal pelvis, 3 cm in the major diameter, macroscopically, infiltrating the renal parenchyma and the adipose peri-hilar tissue. The histological examination demonstrated a high-grade neuroendocrine carcinoma (Fig. 1 and Fig. 2) with vascular invasion and elevated Ki-67 proliferative index (80%), associated with a high-grade urothelial carcinoma (according to WHO, 2004). Infiltration of the renal parenchyma and fat tissue was histologically confirmed (TNM stage pT3). The tumor was associated with interstitial peritumoral nephritis and nephrogenic metaplasia of the superior calyces. Ureteral and vascular margins were free from neoplasia. The neuroendocrine nature of the tumor was confirmed by immunocytochemistry, with positive staining to Chromogranin A, Synaptophysin and CD56; high molecular weight keratins (34-E12) was expressed in the urothelial but not in 58
Fig. 2 - At higher magnification, the neuroendocrine cells in the lower part of the picture demonstrated highly basophylic nuclei with apoptotic bodies and scanty cytoplasm, while atypical urothelial cells in the upper part are characterized by bigger nucleolated nuclei and more abundant eosinophilic cytoplasm. H&E, 400×.
Fig. 3 - Immunocytochemical panel showing expression of high molecular weight keratins 34-E12 in the urothelial but not in the neuroendocrine cells (A), while neuroendocrine markers CD56 (B), Chromogranin A (C) and Synaptophysin (D) are positive only in the neuroendocrine component of the tumor. 200×.
the neuroendocrine cells; conversely, urothelial cells were negative to neuroendocrine markers (Fig. 3). Following nephroureterectomy, the patient was referred to our oncological department. Due to his cardiac comorbidities and his poor prognosis, the patient did not undergo chemotherapy. He died 4 months after surgery because of the disease.
© 2013 Wichtig Editore - ISSN 0391-5603
Palumbo et al
Discussion Neuroendocrine tumors are malignant tumors arising from enterochromaffin or amine precursor uptake and decarboxylation (APUD) cells. Neuroendocrine tumors most commonly involve the gastrointestinal tract, which account for approximately 70% of all cases, and the respiratory system. This kind of neoplasms is rarely observed in the urinary tract (2). Primary renal neuroendocrine tumors are extremely rare lesions and their origin is still uncertain because neuroendocrine cells are not present in the normal renal parenchyma, pelvis and ureter; on the other hand, these cells are present in the bladder and prostate. The most popular hypothesis about the origin of primary renal neuroendocrine tumors is that primary renal neuroendocrine tumors arise from totipotential primitive stem cells capable of neuroendocrine, mesenchymal and epithelial differentiation (3). Neuroendocrine tumors of the kidney are subdivided into epithelial and neural types (4). Neural types of renal NE tumors include primitive neuroectodermal tumor, neuroblastoma and paraganglioma and usually arise in the renal parenchyma. Epithelial neoplasms usually arise in the renal pelvis, and are divided in carcinoid tumor, small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma. They can be associated with other types of tumors such as transitional cell carcinoma, adenocarcinoma and squamous cell carcinoma (5). Actually, about 90 cases were reported in literature and, to the best of our knowledge, only 5 cases of large cell renal NE tumor have been reported to date. Most patients presented in the fourth to seventh decade with abdominal, back or flank pain, accompanied by hematuria and fever, even if about 25-30% of renal neuroendocrine tumors are incidentally detected. Symptoms of the
REFERENCES 1.
2. 3.
carcinoid syndrome are uncommon and they are seen in less than 10% of all cases (6). Large cell renal NE tumors seem to have an aggressive course and a worse prognosis. At the diagnosis, the patients were asymptomatic or had aspecific symptoms, despite the tumor had a local invasion and presented an advanced pathological stage at histological examination. The patients died within few months after surgery, despite radical surgery.
Conclusions Large cell renal neuroendocrine carcinoma is a highly aggressive tumor and patients often present with locally advanced disease. In conclusion, we described a case of large cell neuroendocrine carcinoma of the renal pelvis. There is still a small number of studies reported in literature; therefore, it is difficult to assess the biological behavior and the potential prognostic factors of these tumors. Disclaimers Informed consent: The manuscript does not report the results of an experimental investigation on human subjects. Financial support: No financial support (grants and funds) received in support of the study. Conflict of interest: None. Corresponding Author: Carlotta Palumbo, MD Clinica Urologica I, Università degli Studi di Milan IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano Via della Commenda, 15 20122 Milan, Italy [email protected]
4.
Kloppel G. Tumour biology and histopathology of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. 2007;21:15-31. Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med. 1999;340:858-68. Lane BR, Chery F, Jour G, et al. Renal neuroendocrine tumours: a clinicopathological study. BJU Int. 2007;100:1030-1035.
5.
6.
Dundr P, Pešl M, Povýšil C, et al. Primary large cell neuroendocrine carcinoma of the kidney. Pathol. Oncol. Res. 2010; 16:139-142. Mazzucchelli R, Morichetti D, Lopez-Beltran A, et al. Neuroendocrine tumours of the urinary system and male genital organs: clinical significance. BJU Int. 2009;103(11):1464-70. Murali R, Kneale K, Lalak N, Delprado W. Carcinoid tumors of the urinary tract and prostate. Arch Pathol Lab Med. 2006;130:1693-706.
© 2013 Wichtig Editore - ISSN 0391-5603
59
Copyright of Urologia is the property of Wichtig Editore and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
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