|Year : 2010 | Volume
| Issue : 3 | Page : 367-369
Adult neuroblastoma of the ovary: A rare tumor with review of literature
Meeta Singh, Prerna Arora, Sarita Singh, Sangeeta Bohara, Nita Khurana, Vijay Zutshi, Rishi Kumar
Department of Pathology, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India
|Date of Web Publication||29-Nov-2010|
Room No. 62, Department of Pathology, Maulana Azad Medical College, Bahadur Shah Zafar Marg, New Delhi-110002
Source of Support: None, Conflict of Interest: None
Neuroblastoma is a tumor of pediatric age group and is extremely rare in adults. Common sites involved in adults are almost similar to that seen in children like retroperitoneum, adrenal gland, pelvis and mediastinum. Ovarian neuroblastoma has never been reported in the literature before. We, hereby, present a case of a 38-year-old lady with bilateral ovarian neuroblastoma diagnosed as Krukenberg's tumor clinicoradiologically.
Keywords: Neuroblastoma, ovarian, adults
|How to cite this article:|
Singh M, Arora P, Singh S, Bohara S, Khurana N, Zutshi V, Kumar R. Adult neuroblastoma of the ovary: A rare tumor with review of literature. J Can Res Ther 2010;6:367-9
|How to cite this URL:|
Singh M, Arora P, Singh S, Bohara S, Khurana N, Zutshi V, Kumar R. Adult neuroblastoma of the ovary: A rare tumor with review of literature. J Can Res Ther [serial online] 2010 [cited 2020 Jan 28];6:367-9. Available from: http://www.cancerjournal.net/text.asp?2010/6/3/367/73367
| > Introduction|| |
Neuroblastoma is derived from primitive neural crest cells of the adrenal medulla and is the fourth most common malignancy of childhood.  More than 90% of cases occur in patients younger than 10 years and it is extremely rare in adults. Common sites involved are almost similar to children like retroperitoneum, adrenal gland, pelvis and mediastinum. Ovarian neuroblastoma has never been reported in the literature before.
We, hereby, present a case of a 38-year-old lady with bilateral ovarian neuroblastoma diagnosed as Krukenberg's tumor clinicoradiologically.
| > Case Report|| |
A 38-year-old lady presented with weight loss for past 2 months. On examination she had ascites. Ultrasound and CECT showed large bilateral adnexal masses with heterogenous enhancement [Figure 1]. A diagnosis of Krukenberg's tumor was suggested and a search for primary was advised. The patient was thoroughly investigated for a possible primary in the G.I tract, pancreas, gall bladder, breast and elsewhere without yielding any results. Serum CA-125, LDH, AFP, HCG and CEA were within normal limits.
|Figure 1: CECT abdomen showing large bilateral pelvic masses, inset showing normal bilateral adrenals and retroperitoneum|
Click here to view
Patient underwent total abdominal hysterectomy with bilateral salphingo-oophorectomy with pelvic lymphadenectomy. Laparotomy revealed deposits in peritoneum.
Grossly both the ovaries were enlarged measuring 10×8×6 cm on right side and 13×9×8 cm on left side [Figure 2]. The surface of right-sided ovary was lobulated while left was round and solid [Figure 2]. Cut section of both ovaries was solid grey-white glistening with large areas of hemorrhage and necrosis [Figure 2] Microscopically, the masses were composed uniformly of malignant small round cells present in lobules and interspersed in an abundant fibrillary background with focal rosetting [Figure 3]. Exhaustive multiple sections examined from the tumor failed to reveal any coexistent germ cell tumor, mucinous areas or any other neuroectodermal element. Serosal aspect also showed tumor deposits [Figure 4].
|Figure 2: Gross appearance of bilateral ovarian masses with hysterectomy. Arrow showing the lobulated surface of right ovarian mass. Inset showing cut-section of left ovary|
Click here to view
|Figure 3: Poorly differentiated neuroblastoma with mats of neuropil and focal resetting (arrow) (H and E, 400×)|
Click here to view
|Figure 4: Scanner view showing surface deposits of neuroblastoma (arrow) on the ovary (H and E, 40×)|
Click here to view
Immunohistochemistry showed cells to be positive for anti-S-100 [Figure 5]a, anti-synaptophysin [Figure 5]b, anti-neuron specific enolase [Figure 5]c and focal anti-chromogranin [Figure 5]d. Thus, based on above findings a diagnosis of neuroblastoma ovary, poorly differentiated type, possibly metastatic (bilateral with lobulated surface) was made.
|Figure 5: Immunohistochemistry- A: S-100; B: Synaptophysin; C: NSE; D: Chromogranin. (Immunohistochemistry: Avidin-biotin method with DAB Chromogen and Hematoxylin counterstain, 400×)|
Click here to view
The patient was rigorously investigated for primary in adrenal, retroperitoneum [Figure 1], nose, head and neck, mediastinum and extremities but no primary was found any where. Urinary VMA was found to be raised.
Considering all the aspects; a diagnosis of primary in one ovary with metastasis to other was made. Another possibility of metastatic neuroblastoma from a regressing primary elsewhere was also kept.
| > Discussion|| |
The incidence of neuroblastoma in adults (ANB) is 0.2 cases per million person-years which makes it an extremely rare tumor of this age group.  The most common site of neuroblastomas in children is the adrenal medulla. While in adults, considering the last 30 reported cases (>18 yrs), ,,,,, extra adrenal sites are more common like retroperitoneum (30%) followed by adrenal, pelvis and mediastinum, other rare sites include head and neck, mesentery, thoracic spine, epidural space and extremities. There has been a single case report of ovarian metastasis (unilateral) with primary in the adrenals.  Ovarian involvement with no primary elsewhere leading to presentation as bilateral pelvic masses with ascites is a unique feature of this case.
The mean age of presentation in various studies has been 38-49 years with equal incidence in both males and females.
Krukenberg's tumor is considered the most common cause for bilateral solid ovarian tumor followed by several surface epithelial tumors and germ cell tumors and these possibilities were considered in this case.
In adults, neuroblastoma in ovary occurs under specific conditions like, as a neuroepithelial component in a pre-existing immature or mature teratoma or as a part of primary neuroectodermal tumors (PNET) of the ovary. , Primary ovarian neuroblastoma is distinguished from the former condition by demonstration of additional components like skin, hair or cartilage. PNET of the ovary are composed exclusively or almost exclusively of neuroectodermal elements,  neuroblastoma is known to occur in this setting but other neuroectodermal elements like epindymoma, medulloblastoma or rarely scarce teratomatous component are usually found to coexist. Rare cases show pure neuroblastoma without any other component but later on autopsy adrenal revealed the primary. 
On microscopic examination neuroblastoma is composed of sheets of small round cells. Owing to this morphology it enters the differential diagnosis of other small round cell tumors more common in this age group and can add to the diagnostic difficulties. These include malignant lymphoma, PNET/Ewings sarcoma (PNET/ES), desmoplastic small round cell tumor and metastatic small-cell carcinoma all of which are known to occur in similar sites including ovary. Others like juvenile granulosa cell tumor, primitive germ cell tumor and small-cell carcinoma (pulmonary type and hypercalcemic type) were also considered in this case. Immunohistochemistry plays a major role in arriving at a diagnosis in such a situation. In our case, leukocyte common antigen and CD99 were negative ruling out lymphoma and PNET/ES, respectively. Cytokeratin and epithelial membrane antigen were also negative ruling out epithelial origin.
A study demonstrated that MYCN oncogene amplification was rare in ANB as opposed to 20-30% of pediatric neuroblastomas.  This may be a part of different biological behaviour, including the slower progression of ANB.
Because of rarity of these cases, risk stratification and staging of ANB is done like pediatric ones. In a study by Hasegawa et al.  patients with undifferentiated ANB died shortly after diagnosis or discovery of disease; however, those with poorly differentiated ANB had an extended survival. In another study that compares adult with pediatric neuroblastoma showed that adults have a worse long-term prognosis regardless of stage or site. Although the early survival at 2-3 years is actually better due to the more indolent course in patients with local or regional disease but ultimate survival is <5%.  The risk-based approach may be inappropriate in patients with adult neuroblastoma because of the much worse prognosis of adults with localized neuroblastoma compared with children with similar involvement.  It is possible that in ANB more aggressive initial therapy including radiation and chemotherapy may be of benefit, even in patients with low-stage disease. 
Another interesting phenomenon highlighted by this case is a possibility of it being a secondary from a regressing primary elsewhere. Spontaneous regression by neuroblastoma is a well-known phenomenon seen in children. , A regression of primary in a metastatic neuroblastoma is extremely rare with scattered case reports in the past observed in children. It has never been observed in adults.
| > References|| |
|1.||Kushner BH, Cheung NK Neuroblastoma - from genetic profiles to clinical challenge. N Engl J Med 2005;353:2215-7. |
|2.||McLean TW, Iskandar SS, Shimada H, Hall MC. Neuroblastoma in an adult. Urology 2004;64:1232. |
|3.||Hasegawa T, Hirose T, Ayala AG, Ito S, Tomaru U, Matsuno Y, et al. Adult neuroblastoma of the retroperitoneum and abdomen: clinicopathologic distinction from primitive neuroectodermal tumor. Am J Surg Pathol 2001;25:918-24. |
|4.||Cowan JM, Dayal Y, Schwaitzberg S, Tischler AS. Cytogenetic and immunohistochemical analysis of an adult anaplastic neuroblastoma. Am J Surg Pathol 1997;21:957-63. |
|5.||Franks LM, Bollen A, Seeger RC, Stram DO, Matthay KK. Neuroblastoma in adults and adolescents: an indolent course with poor survival. Cancer 1997;79:2028-35. |
|6.||Argani P, Erlandson RA, Rosai J. Thymic neuroblastoma in adults: report of three cases with special emphasis on its association with the syndrome of inappropriate secretion of antidiuretic hormone. Am J Clin Pathol 1997;108:537-43. |
|7.||Tateishi U, Hasegawa T, Makimoto A, Moriyama N. Adult neuroblastoma: radiologic and clinicopathologic features. J Comput Assist Tomogr 2003;27:321-6. |
|8.||Aguirre P, Scully RE. Malignant neuroectodermal tumor of the ovary, a distinctive form of monodermal teratoma: report of five cases. Am J Surg Pathol 1982;6:283-92. |
|9.||Block M, Gilbert E, Davis C. Metastatic neuroblastoma arising in an ovarian teratoma with long-term survival. Case report and review of the literature. Cancer 1984;54:590-5. |
|10.||Kleinman GM, Young RH, Scully RE. Primary neuroectodermal tumors of the ovary. A report of 25 cases. Am J Surg Pathol 1993;17:764-78. |
|11.||Matthay K, Seeger RC, Haase GM, Stram DO, O'Leary M. Treatment and outcome for stage III neuroblastoma based on prospective biologic staging. Med Pediatric Oncol 1994;23:173. |
|12.||Hero B, Simon T, Spitz R, Ernestus K, Gnekow AK, Scheel-Walter HG. Localized infant neuroblastomas often show spontaneous regression: results of the prospective trials NB95-S and NB97. J Clin Oncol 2008;26:1504-10. |
|13.||Yamamoto K, Hanada R, Kikuchi A, Ichikawa M, Aihara T, Oguma E, et al Spontaneous regression of localized neuroblastoma detected by mass screening. J Clin Oncol 1998;16:1265-9. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]