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Adult pelvic neuroblastoma: long-term survival and review of the literature / Eriskinlerde pelvic noroblastom: Uzun donem sagkalim ve literaturun gozden gecirilmesi.


Here, we report a 52-year-old man with pelvic neuroblastoma; to our knowledge, he is the oldest patient reported in the literature. A large retroperitoneal pelvic tumor was located between the bladder and rectum without any invasion to the adjacent organs. A 24-hour urine catecholamine examination revealed that vanillin mandelic acid excretion was above the normal range. The tumor was resected without any pelvic organ injuries. Histopathology showed pleomorphic cells with spindle-shaped vesicular nuclei. The immunostaining results for NB84. bc1-2. neuron-specific enolase, and CD56 were positive. CD99 showed weak cytoplasmic staining, which is consistent with a primitive neural or neuroectodermal-type neoplasm. However. NB84 positivity and an intact Ewing sarcoma gene locus (EWS) locus using fluorescence in situ hybridization analysis implied neuroblastoma. Appropriate immunohistochemical studies distinguished adult neuroblastoma from other differential diagnoses, especially primitive neuroectodermal tumor. Despite the low stage of the tumor, the patient's age and the large size of the tumor necessitated 6 cycles of adjuvant combination chemotherapy. Radiotherapy was not indicated for the patient, but he was followed regularly by pelvic computed tomography. This patient has benefited from a tumor-free survival for up to 6 years. Neuroblastoma is a differential diagnosis in patients with a pelvic mass, and treatment may be given according to pediatric protocols.

Key words: Adult neuroblastoma; NB84: neuroblastoma staging systems; pelvic mass: survival.

Submitted (Gelis tarihi): 15.05.2010


Burada, bildigimiz kadariyla literaturde bildirilen en yasli vaka olan 52 yainda pelvik noroblastomu olan erkek hastayi sunuyoruz. Hastada mesane ve rektum arasinda cevre organlara yayilimi olmayan buyuk bir retroperitoneal pelvik tumor mevcuttu, ldrarda 24-saatlik katekolamin degerlendirmesinde vanilin mandelik asit atilimi normal sinirin uzerinde idi. Tumor herhangi bir pelvik organ hasan olmaksizin cikarildi. Histopatolojik degerlendirmede ig-sekilli vezikuler nukleusu olan pleomorfik hucreler goruldu. NB84, bc1-2. noron-spesifik enolaz, ve CD56 icin immunboyama sonuclari pozitif idi. Primitif noral veya noroektodermal tip tumorler ile uyumlu olarak CD99 zayif sitoplazmik boyama gosterdi. Ancak. NB84 pozitifligi ve floresan in situ hibridizasyon analizi kullanilarak elde edilen intact Ewing sarkomu gen lokusu noroblastomayi dusundurdu Uygun histokimyasal calismalar yetiskin noroblastomayi diger ayirici tanilardan, ozellikle primitif noroektodermal tumorden ayirmaktadir. Tumorun dusuk evresi, hastanin yasi ve buyuk tumor boyutu, 6 kur adjuvan kombine kemoterapi gerektirmistir. Radyoterapi endikasyonu yoktur. ancak hasta duzenli olarak pelvik bilgisayarli tomografi ile izlenmiur. Hastanin 6 yila kadar tumorsuz sagkalim avantaji olmusur. Pelvik kitlesi olan hastalarda noroblastom ayirici tanida dusunulmelidir ve tedavi pediatrik protokoller gore verilebilir.

Anahtar sozcukler: NB84: noroblastom evreleme sistemleri: pelvik kitle; sagkalim; yetiskin noroblastomu.

Accepted after revision (Duzeltme sonrasi kabul tarihi): 22.07.2010

Neuroblastoma, which is a neural crest cell-derived tumor, rarely occurs in adulthood, but it is one of the most common solid tumors in children. Less than 10% of patients are older than 10 years. (1), (2) Pelvic neuroblastoma is an unusual tumor (5% of all neuroblastoma types) with a much more favorable prognosis than abdominal neuroblastoma. Several cases of malignant pheochromocytoma of the urinary bladder have been reported, but few cases of adult pelvic neuroblastoma have been reported in the literature. (3-5)

Currently, there is no standard treatment guideline for adult-onset neuroblastoma. Despite treatment with standard children's protocols, adult survival is poor, especially patients with localized disease have a more aggressive course than children. (6)

Surgical resection of pelvic neuroblastoma is a technical challenge, but the complete removal of the tumor plays a major prognostic role in localized treatment. (6)

When an adult presents with a large solid pelvic mass, neuroblastoma should be considered as a part of the differential diagnosis, although this diagnosis is ultimately rare. If neuroblastoma is confirmed, tissues should be evaluated using histopathological examination in accordance with the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Risk Group Staging System (INRGSS). (7)

To the best of our knowledge, our case of pelvic neuroblastoma is the oldest patient reported in the literature who has presented with a pelvic mass that was treated using a complete en-bloc resection and adjuvant chemotherapy.

Case report

A 52-year-old man was admitted to our general hospital in April 2004 complaining of recent night sweats and low back pain in the sacrum that radiated to the back of thighs. He had a history of diabetes mellitus with initiation of occasional dysuria, constipation and a 7 kg weight loss over 2 years. Physical examination was normal except for a palpable pelvic mass during abdomino-pelvic and digital rectal examinations. Laboratory tests, including prostate spesific antigen (PSA), lactate dehydrogenase (LDH), routine hematological tests, and blood chemistry, were normal except for microscopic hematuria.

Pelvic and abdominal ultrasonography depicted a solid, heterogeneous, lobulated, and calcified mass that was 187x145x104 mm. Barium enema was normal except for an inferolateral shift of the colon. Voiding cystourethrogram confirmed the displacement of the bladder and urethral elongation. An abdominopelvic computed tomography (CT) confirmed that a pelvic tumor was located between the bladder and rectum, which displaced the bladder to the right side; no tumor invasion or abnormal abdominopelvic lymph nodes were observed (Fig. la).


Bone marrow biopsy showed no evidence of metastatic disease, and a whole-body metaiodobenzylguanidine (MIBG) diagnostic scan was also normal. The 24-hour urine catecholamine examination showed that vanillin mandelic acid (VMA) was over the normal range (23 nig, normal range 0.5-12 mg).

Under general anesthesia, a retroperitoneal pelvic tumor was observed through a lower midline abdominal incision. The tumor was resected from the bladder and prostate without any invasion into adjacent organs during a 5-hour operation. An examination of the fresh frozen specimen examination revealed that resected margins were tumor-free without abnormal pelvic lymph nodes (Fig. lb).

The postoperative urine VMA levels were reduced to 12.9 mg after 2 days. Primary histological examination of the resected tumor showed a neurological differentiation. Both primitive neuroectoderm and sympathicoblastoma were proposed as diagnoses.

The patient was referred to the Sarcoma Unit, Royal Marsden Hospital, London, England, for a second opinion and further management. A histological review of tumor sections showed a cellular neoplasm that was composed of pleomorphic cells with spindle-shaped vesicular nuclei. Many cells showed indented nuclei and an abundant fibrillary matrix with a rosette pattern, which is consistent with a neurological differentiation. Immunostaining results for NB84, bcl-2, neuron-specific enolase (NSE) and CD56 were positive. CD99 showed weak cytoplasmic positivity, and smooth muscle actin (SMA), desmin, synaptophysin, chromogranin, S100 protein, cytokeratin AEl/AE3, CD45, CD34, CD117, calretinin, calponin,13-catenin, epithelial membrane antigen (EMA), and Cam5.2 were all negative. Reticulin showed a nested pattern.

This was not a germ cell tumor histopathologically, and the markers were not typical for Ewing's family tumors. These primitive neural or neuroectodermal neoplasmic features coupled with NB84 positivity implied a neuroblastoma (Fig. 2). Based on the INRGSS factors in this patient, the MYCN status was not amplified because 11q and lp were normal.

The patient received 6 cycles of vincristine 2 mg, dacarbazine 600 mg/[m.sup.2] per day on days 1 and 2, and cyclophosphamide 800 mg/[m.sup.2] on day 1. The vincristine and dacarbazine regimen was repeated 4 additional times every 3 weeks.



To the best of our knowledge, this patient is one of the oldest patients with neuroblastoma. There has been a steady decline in the incidence of adult neuroblastoma from 0.47 cases per million per year in 1973-1977 to 0.12 cases per million per year in 1998-2002.141Adults with neuroblastoma have a significantly worse outcome than children. This may be due to tumor biology, a more virulent clinical course, or the fact that adults are less sensitive or have poor tolerance to pediatric chemotherapy regimens. Neuroblastoma is diagnosed more frequently in advanced stages in adolescence and has common sites of metastases compared to children. (5)

The observed 3- and 5-year survival rates were the lowest among adults (45.9% and 36.3%, respectively), but 86% and 84.6% of infants survived for 3 and 5 years. A long-term evaluation of adult neuroblastoma survival in a 10-year follow-up study revealed a continuous decrease in survival during the first 7 years after diagnosis. (5)

Although the location of the tumor (pelvic), negative chromogranin, and synaptophysin make the diagnosis of neuroblastoma controversial, other differential diagnoses, such as a sarcoma with neuroectodermal differentiation, was not ruled out.

Because CD99 showed weak cytoplasmic positivity, Fluorescent In Situ Hybridization (FISH) analysis was performed to investigate the presence of Ewing sarcoma gene locus (EWS) translocation, which suggests Primitive Neuroectodermal Tumors (PNET) (8) as a differential diagnosis. However, FISH analysis showed an intact EWS locus. The undifferentiated subtype had ultrastructural features with the neurological characteristics of neuroblastoma and lacked a chimeric transcript (EWS-FLI1 or ERG) that is specific for PNET.

Based on histopathological studies, the patient's condition, and genetic characteristics, the tumor could be classified as an INSS stagel tumor. Although surgery alone is sufficient for stage1 neuroblastoma, and chemotherapy is not highly recommended in this stage, microscopic disease may remain after surgery. Furthermore, tumor size suggests an "advanced-stage status in other staging systemsm The frequent late local and regional recurrences that are seen in these adult tumors compared to pediatric tumors should also be considered. As a result of all of these reasons, and because chemotherapy may benefit individual patients especially when there have been very few treated patients reported in the literature with adult-onset neuroblastoma, we decided to perform primary chemotherapy in this patient. Nevertheless, a negative whole-body scan and a lack of the usual indications for radiotherapy for localized, inoperable primary or painful metastases convinced us that radiotherapy was unnecessary. We monitored the patient closely using regular imaging to identify any early recurrence of tumor using a whole-body MIBG diagnostic scan and a whole-body indium-1 1 1 octreotide scan. If the disease recurred despite adjuvant treatment, one should investigate whether the tumor concentrated MIGB or somatostatin analogues, and the tumor might be susceptible to targeted radioisotope therapy. These investigations have remained negative 6 years after the initial surgery.

As a conclusion, neuroblastoma should be considered in almost all eases of abdominopelvic masses, although its incidence is rare in adulthood. Moreover, if a pathological examination confirms a diagnosis of neuroblastoma, treatment may be performed based on pediatric guidelines because there are no principles for the treatment of adult-onset neuroblastoma. Surgical resection of the tumor followed by chemotherapy provided a satisfactory long-term survival in our adult neuroblastoma case. However, adult patients need regular follow-up investigations because of the frequent recurrence of these tumors compared to pediatric tumors.

Conflict of interest

No conflict of interest was declared by the authors.

Correspondence (Yazisma): Prof. Dr. Abdol Mohammad Kajbafzadeh. 7th Street, No. 34, 2nd Floor, Saadat-abad, Ave 199871, Tehran, Iran. Phone: 0098-21-22069451 e-mail:


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(2.) Gaspar N, Hartmann 0, Munzer C, Bergeron C, Millot F, Cousin-Lafay L, et al. Neuroblastoma in adolescents. Cancer 2003;98:349-55.

(3.) Hasegawa T. Hirose T, Ayala AG, Ito S, Tomaru U, Matsuno Y, et al. Adult neuroblastoma of the retroperitoneum and abdomen. Am J Surg Pathol 2001;25:918-24.

(4.) MeyerJJ, Sane SM, Drake RM. Malignant pa raganglioma heochromocytoma of the urinary bladder. Pediatrics 1979;63:879-85.

(5.) Esiashvili N, Goodman M, Ward K, Marcus RB, Johnstone PAS. Pediatr neuroblastoma in adults: incidence and survival analysis based on SEER data. Pediatr Blood Cancer 2007;49:41-6.

(6.) Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V. Castelberry RP, et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 1993;11:1466-77.

(7.) Cohn SL, Pearson AD, London WB, Moneta ir T, Am bros PF, Brodeur GM, et al. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol 2009;27:289-97.

(8.) Mhawech-Fauceglia P. Herrmann F, Penetrante R, Beck A. Sait S. Block AM, et al. Diagnostic utility of FLI-1 monoclonal antibody and dual-colour, break-apart probe fluorescence in situ (FISH) analysis in Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET). A comparative study with CD99 and FLI-1 polyclonal antibodies. Histopathology 2006;49:569-75.

(9.) Kushner BH, Kramer K, LaQuaglia MP, Modak S Cheung NK. Neuroblastoma in adolescents and adults the Memorial Sloan-Kettering experience. Med Pediat Oncol 2003;41:508-15.

Abdol Mohammad Kajbafzadeh (1), Zhina Sadeghi (1), Shadi A. Esfahani (1), Cyril Fisher (2), Ian Judson (2)

Tehran University of Medical Sciences. Pediatric Urology Research Center, Urology Department, Tehran, Iran :Royal Marsden Hospital. Pathology Department, Sarcoma Unit. London. England
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Title Annotation:Case Report / Olgu Sunumu
Author:Kajbafzadeh, Mohammad; Sadeghi, Zhina; Esfahani, Shadi A.; Fisher, Cyril; Judson, Lan
Publication:Turkish Journal of Urology
Date:Jun 1, 2011
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