Introduction:Ganglioneuroblastoma is a rare peripheral neuroblastic tumor that is derived from developing neuronal cells of the sympathetic nervous system, and is found mostly, but not exclusively, in babies and young children.
Case Presentation:
To the best of our knowledge, there have been no previously reported cases of ganglioneuroblastoma of the mediastinum from Pakistan. We present a case of ganglioneuroblastoma in an eight-year-old Pakistani Sindhi boy incidentally found to have a large posterior mediastinal mass that on biopsy initially looked like ganglioneuroma. He underwent successful excision of the mediastinal mass and remained stable post-operatively. Final pathology findings showed a ganglioneuroblastoma. He has remained free of symptoms on long-term follow-up.
Conclusions:
The rarity of this tumor along with its almost exclusive occurrence in the pediatric population necessitates a thorough investigation of Patients presenting with a symptomatic mass

Ashfaq, Awais

Bawany, Samira A

Fatimi, Saulat

PubMed

Abstract Introduction Ganglioneuroblastoma is a rare peripheral neuroblastic tumor that is derived from developing neuronal cells of the sympathetic nervous system, and is found mostly, but not exclusively, in babies and young children. Case presentation To the best of our knowledge, there have been no previously reported cases of ganglioneuroblastoma of the mediastinum from Pakistan. We present a case of ganglioneuroblastoma in an eight-year-old Pakistani Sindhi boy incidentally found to have a large posterior mediastinal mass that on biopsy initially looked like ganglioneuroma. He underwent successful excision of the mediastinal mass and remained stable post-operatively. Final pathology findings showed a ganglioneuroblastoma. He has remained free of symptoms on long-term follow-up. Conclusions The rarity of this tumor along with its almost exclusive occurrence in the pediatric population necessitates a thorough investigation of patients presenting with a symptomatic mass.</p

Bawany Samira A

Fatimi Saulat H

Ashfaq Awais

Directory of Open Access Journals

Journal of Medical Case Reports

Ganglioneuroblastoma of the posterior mediastinum: a case report

Saulat H Fatimi

Samira A Bawany

Awais Ashfaq

Springer - Publisher Connector

eCommons@AKU

CASE REPORT Open AccessGanglioneuroblastoma of the posteriormediastinum: a case reportSaulat H Fatimi1, Samira A Bawany2 and Awais Ashfaq2*AbstractIntroduction: Ganglioneuroblastoma is a rare peripheral neuroblastic tumor that is derived from developingneuronal cells of the sympathetic nervous system, and is found mostly, but not exclusively, in babies and youngchildren.Case presentation: To the best of our knowledge, there have been no previously reported cases ofganglioneuroblastoma of the mediastinum from Pakistan. We present a case of ganglioneuroblastoma in an eight-year-old Pakistani Sindhi boy incidentally found to have a large posterior mediastinal mass that on biopsy initially looked likeganglioneuroma. He underwent successful excision of the mediastinal mass and remained stable post-operatively. Finalpathology findings showed a ganglioneuroblastoma. He has remained free of symptoms on long-term follow-up.Conclusions: The rarity of this tumor along with its almost exclusive occurrence in the pediatric populationnecessitates a thorough investigation of patients presenting with a symptomatic mass.IntroductionGanglioneuroblastoma is a rare variety of peripheral neuro-blastic tumor (neuroblastoma) that can arise anywherealong the sympathetic nervous system. It occurs almostexclusively in the pediatric population, with some reportedcases in the adult population. It is the third most commonchildhood malignancy after leukemia and brain tumors,and is the commonest solid extracranial tumor among chil-dren [1]. Its true global incidence, however, is unknown.According to the Surveillance, Epidemiology and EndResults (SEER) Registry maintained by the National CancerInstitute, the annual incidence of neuroblastoma is 7.6 per1,000,000 population in the USA [2]. Of these cases, nostatistics regarding the subtype of ganglioneuroblastomaare available. Here, we present the case of an eight-year-oldpreviously healthy boy who presented to our clinic withnon-specific signs and symptoms of pain and was laterdiagnosed to have ganglioneuroblastoma.Case presentationAn eight-year-old otherwise previously healthy PakistaniSindhi boy presented to our clinic with complaints ofright-sided lumbar pain for a week. At initial clinicalassessment our patient’s weight was 36.3 kg and hisheight was 142 cm. His overall nutritional status wasgood and had a normal height and build for his age withno history of weight loss. He had no other associatedcomorbidities. His family history was significant for dia-betes mellitus, hypertension and untreated pancreaticcancer and renal cancer. The rest of his history and testresults were unremarkable. A physical examination wasgrossly unremarkable. Ultrasound of the abdomen wasperformed, with normal results. A chest X-ray was per-formed that showed a homogenous soft tissue densitymass in the posterior mediastinum with no evidence ofrib erosion. To evaluate the mass further, an MRI wasperformed (Figure 1). The dimensions of the mass were7.3 × 6.0 cm.A computed tomography (CT)-guided biopsy of themass was advised, which was carried out under generalanesthesia. No complications were observed after theprocedure and a post-procedural CT scan did not revealany pneumothorax. Histopathology of the biopsy materialshowed multiple cones of tissue exhibiting spindle-shaped cells arranged haphazardly, having moderatecytoplasm and wavy spindle shaped nuclei. Scatteredmature ganglion cells were also identified, characterizedby abundant cytoplasm and round to oval nuclei; as suchno immature element was identified nor was there any* Correspondence: ashfaq.awais@gmail.com2Aga Khan University, Stadium Road, Karachi 74800, PakistanFull list of author information is available at the end of the articleFatimi et al. Journal of Medical Case Reports 2011, 5:322http://www.jmedicalcasereports.com/content/5/1/322 JOURNAL OF MEDICALCASE REPORTS© 2011 Fatimi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.evidence of increased mitosis or areas of necrosis. Thespecimen was also treated with immunohistochemicalstains and was found to be positive for S-100, synapto-physin, chromogranin, and leucocyte common antigen(LCA). These morphological and immunohistochemicalfindings were consistent with a diagnosis of ganglioneur-oma, since no malignant features were identified.In addition, whole body skeletal scintigraphy was per-formed with Tc-99 m for metastatic investigation, whichshowed bilateral symmetrical tracer distribution in boththe axial and appendicular skeleton with no areas ofabnormal tracer accumulation and normal excretion ofthe tracer from both kidneys and urinary bladder.Bone marrow aspirate and trephine from the iliac crestperformed for staging of the tumor showed all three celllines with normal erythroid and myeloid precursors. Thespecimen was stained with hematoxylin and eosin and afew atypical mononuclear cells were noted; however, thesample was inadequate showing mainly cartilage, muscleand clot, and was hence non-diagnostic. There was noth-ing to suggest malignancy or granuloma in the sectionsexamined. It was suggested to repeat an adequate lengthbone marrow trephine if there was a clinical indication todo so.Surgery was planned for resection of tumor. Prior tothat, pre-operative evaluation included a normal com-plete blood count, coagulation profile and serum lactatedehydrogenase levels. Surgery was approached using leftthoracotomy. After entering the chest cavity, tumor wasexcised from the aorta, subclavian vessels and vertebralcolumn. After adequate hemostasis, chest tubes wereplaced and routine closure of thoracotomy was carriedout. The resected mass measuring 9.5 × 7 × 4.5 cm wassent for histopathology that confirmed the pre-operativediagnosis and presence of tumor-free margins.Post-operatively, our patient remained hemodynami-cally stable. He received intravenous antibiotics and epi-dural marcaine infusion for pain relief, which wasswitched over to oral antibiotics and intravenous analge-sics. Our patient was running a fever by the third post-operative day, which was followed by a transient episodeof desaturation; however this improved without conse-quence. A post-operative chest X-ray was also unre-markable. On the fourth post-operative day our patientwas discharged from the hospital on oral augmentin andnon-steroidal anti-inflammatory drugs (NSAIDs) forpain. At discharge, the wound was clean, healing andhealthy.At follow-up a week later our patient’s condition wasstable. The final post-resection histopathology reportshowed a circumscribed and partially capsulated neo-plasm composed of spindle cells arranged irregularly inshort fascicles, scattered ganglion cells and abundantcytoplasm. Some nodules within the mass showed small,round neoplastic cells, scant cytoplasm, increasednuclear to cytoplasmic ration and hyperchromaticnuclei. The mitotic rate was identified as two to threecells per high-power field and the mitosis karyorrhexisindex (MKI) was < 2%. Focal areas of hemorrhage andnecrosis were also identified. Sections of tissues werealso stained with immunohistochemical stains and werefound to be positive for neurofilament, synaptophysinand chromogranin. The features showed that the tumorwas a ganglioneuroblastoma, nodular type, which arecomposite Schwannian stroma-rich/stroma-dominantand stroma-poor element.At a year later our patient had complaints of somebone pain for which a skeletal survey was performedand was found to be within normal limits. Our patienthas thereafter remained stable.Figure 1 MRI scan showing homogenous soft tissue density mass in the posterior mediastinum. (a) Sagittal section. (b) Axial section.Fatimi et al. Journal of Medical Case Reports 2011, 5:322http://www.jmedicalcasereports.com/content/5/1/322Page 2 of 4DiscussionGanglioneuroblastoma is an uncommon peripheral neuro-blastic tumor. The International Neuroblastoma PathologyClassification, popularly known as the Shimada system,grades these into four distinct categories based upon thehistopathological balance between neural-type cells (primi-tive neuroblasts, maturing neuroblasts, and ganglion cells)and Schwann-type cells (Schwannian-blasts and matureSchwann cells). These include neuroblastomas (Schwan-nian stroma-poor), ganglioneuroblastoma intermixed(Schwannian stroma-rich), ganglioneuroma (Schwannianstroma-dominant) and ganglioneuroblastoma nodular(composite Schwannian stroma-rich/stroma-dominantand stroma-poor) and neuroblastic tumors unclassifiable[3].Ganglioneuroblastoma have intermediate malignantpotential, between that of neuroblastomas and ganglio-neuromas. Histologically, they are considered malignantbecause they contain primitive neuroblasts along withmature ganglion cells. In contrast, their benign counter-parts, ganglioneuromas are fully differentiated tumorsthat contain all mature cell types but lack the immatureelements (such as neuroblasts), atypia, mitotic figures,intermediate cells, or necrosis [4].Ganglioneuroblastomas occur with equal frequency inboth the genders and most commonly in babies and inyoung children, with occurrence after 10 years of agebeing extremely rare [4]. They occur most commonly inthe adrenal medulla, extra-adrenal retroperitoneum, andposterior mediastinum, with the neck and pelvis being lesscommon sites of occurrence [5]. Thus, the occurrence of aposterior mediastianal ganglioneuroblastoma in our eight-year-old patient made this a rarity.When dealing with pediatric masses, differentials such asrhabdomyosarcomas, Wilms tumor, germ cell tumors, andso on, should be taken into consideration. Rhabdomyosar-coma is the most common soft tissue sarcoma in childrenand usually originates in the head and neck (28%), extre-mities (24%), and genitourinary (GU) tract (18%). Thecause is unclear; however, several genetic syndromes suchas neurofibromatosis, Li-Fraumeni syndrome, and so on,are associated with it. Symptoms usually depend on thelocation and the tumours usually present as an expandingmass. Wilms tumor, by contrast, is the most common can-cer of the kidneys in children. The majority are unilateral,encapsulated, vascularized, and usually do not cross themidline of the abdomen. They can go undetected early onbecause the tumor can grow large without causing pain.Children usually present with abdominal swelling or bloodin the urine.Patients with ganglioneuroblastoma often presentclinically with pain caused by either the primary tumoror by metastatic disease. Patients with mediastinaltumors can present with stridor and shortness of breathsecondary to tracheal deviation or narrowing. Largethoracic tumors can cause mechanical obstructionresulting in superior vena cava syndrome. Nerve ornerve root compression by the mass can result in per-ipheral neurological signs. Patients with cervical massescan present with Horner’s syndrome [6]. However, inour patient these classical signs and symptoms were notpresent and the only complaint was that of non-specificlumbar pain.Histological confirmation is required for definitive diag-nosis. Tissue is obtained by incisional biopsy of the pri-mary tumor or bone marrow trephine/aspirate in patientssuspected of having metastatic disease in the bonemarrow.The most common site for metastasis in ganglioneuro-blastomas is bone, which may mean patients present withlimping and unexplained irritability (Hutchinson’s syn-drome). Another site of metastasis is the liver. Pepper syn-drome is the presence of large liver metastases in babiessuch that intra-abdominal pressure becomes so high thatthere might be possibility of respiratory compromise. Inchildren younger than a year old, skin metastases are com-mon, which are darkly pigmented masses resembling blue-berries (hence it is called ‘blueberry muffin’ syndrome) [7].In our patient, investigation was performed to rule outmetastasis and was found to be negative.A CT scan is the imaging modality of choice to evalu-ate neuroblastic tumors. There is enough evidence tosuggest that it is superior both in terms of determiningtumor size and other characteristics including organ oforigin, tissue invasion, vascular encasement, lymphade-nopathy, and calcifications [5].The prognosis for patients with localized disease andyounger age is better; several screening programs weredeveloped for the detection of neuroblastoma in infancyby measuring urinary catecholamines [8] but were notassociated with any difference in mortality. As a result,they are not routinely recommended.Age is taken into account when defining neuroblas-toma histology as favorable or unfavorable. The youngerthe age at diagnosis, the better the survival rate [8] withchildren younger than a year old having considerablybetter survival than older children. Even the outcome offavorable or less aggressive neuroblastomas is worse inolder children [9]. Hence, although it is not rare in theliterature to find reports of good outcomes, the excellentresults and successful follow-up in our patient is of sig-nificant note.Mediastinal neuroblastomas are better in terms ofprognosis than abdominal neuroblastomas in thatpatients with the former tend to present earlier whenthe size is still small, and hence complete resection ofFatimi et al. Journal of Medical Case Reports 2011, 5:322http://www.jmedicalcasereports.com/content/5/1/322Page 3 of 4the tumor is possible [10]. Complete excision remainsthe mainstay of therapy of localized mediastinal neuro-blastomas. There are no reports of the recommendedduration of follow-up; however, follow-up is requiredwith chest X-ray. The two-year event-free survival ratesare 85% to 100%; relapses can be salvaged by furthersurgery or chemotherapy [11].Differential markers for distinguishing ganglioneuro-mas from ganglioneuroblastomas at present are notavailable; immunohistochemical stains with antibodiessuch as neurofilament, synaptophysin, chromogranin,s-100 and LCA are generally positive in both ganglio-neuromas and ganglioneuroblastomas [12]. However ithas been shown on post-mortem histopathology speci-mens that an epidermal-growth-factor-like protein calleddelta-like (dlk), which regulates the differentiation ofneuroblastoma cell lines, showed stronger expression inthe ganglioneuroma cell lines and weaker expression inganglioneuroblastoma cell lines [13], probably suggestingthe loss of this differentiation factor in the progresstoward the malignant disease.ConclusionsThe rarity of ganglioneuroblastoma, along with itsoccurrence in the pediatric population, warrants a greatdeal of suspicion when a younger patient presents witha symptomatic mass. Given the wide variety of clinicalsymptoms the tumor can present with, it is essentialthat neuroblastoma remains as one of the differentialdiagnoses while working on such a case.ConsentWritten informed consent was obtained from thepatient’s next-of-kin for publication of this case reportand any accompanying images. A copy of the writtenconsent is available for review by the Editor-in-Chief ofthis journal.Author details1Section of Cardiothoracic Surgery, Department of Surgery, Aga KhanUniversity, Stadium Road, Karachi 74800, Pakistan. 2Aga Khan University,Stadium Road, Karachi 74800, Pakistan.Authors’ contributionsSHF analyzed our patient’s details and was primarily responsible forobtaining the full investigation results, including the surgery performed onour patient. SAB was involved in assisting the primary faculty, obtainingrelevant details about the case and confirming its rarity, and was a majorcontributor to writing the manuscript. AA contributed a significant effort towriting the manuscript and editing the final draft. All authors read andapproved the final manuscript.Competing interestsThe authors declare that they have no competing interests.Received: 20 July 2010 Accepted: 22 July 2011 Published: 22 July 2011References1. Gurney JG, Ross JA, Wall DA, Bleyer WA, Severson RK, Robison LL: Infantcancer in the U.S.: histology-specific incidence and trends, 1973 to 1992.J Pediatr Hematol Oncol 1997, 19:428-432.2. Horner MJ, Ries LAG, Krapcho M, Neyman N, Aminou R, Howlader N,Altekruse SF, Feuer EJ, Huang L, Mariotto A, Miller BA, Lewis DR, Eisner MP,Stinchcomb DG, Edwards BK, (Eds): SEER Cancer Statistics Review, 1975-2006, National Cancer Institute.[http://seer.cancer.gov/csr/1975_2006/].3. Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B, Stram DO,Gerbing RB, Lukens JN, Matthay KK, Castleberry RP: The InternationalNeuroblastoma Pathology Classification (the Shimada system). Cancer1999, 86:364-372.4. Rha SE, Byun JY, Jung SE, Chun HJ, Lee HG, Lee JM: Neurogenic tumors inthe abdomen: tumor types and imaging characteristics. Radiographics2003, 23:29-43.5. Lonergan GJ, Schwab CM, Suarez ES, Carlson CL: Neuroblastoma,ganglioneuroblastoma, and ganglioneuroma: radiologic-pathologiccorrelation. Radiographics 2002, 22:911-934.6. Mugishima H, Sakurai M: Symptoms of neuroblastoma: paraneoplasticsyndrome. In Neuroblastoma.. 1 edition. Edited by: Brodeur GM, Savada T,Tsuchida Y, Voute PA. Amsterdam, The Netherlands: Elsevier Science B.V.;2000:293-296.7. Lucky AW, McGuire J, Komp DM: Infantile neuroblastoma presenting withcutaneous blanching nodules. J Am Acad Dermatol 1982, 6:389-391.8. Spix C, Berthold F, Erttmann R, Fehse N, Hero B, Klein G, Sander J,Schwarz K, Treuner J, Zorn U, Michaellis J: Neuroblastoma screening atone year of age. N Engl J Med 2002, 346:1047-1053.9. Milović I, Sćekić M, Vujić D, Djurisić S, Djokić D: The characteristics ofmediastinal neuroblastoma and perspectives on surgical excision. ActaChirIugosl 2003, 50:103-107.10. Nitschke R, Smith EI, Shochat S, Altshuler G, Travers H, Shuster JJ, Hayes FA,Patterson R, McWilliams N: Localized neuroblastoma treated by surgery: aPediatric Oncology Group Study. J Clin Oncol 1988, 6:1271-1279.11. Molenaar WM, Baker DL, Pleasure D, Lee VM, Trojanowski JQ: Theneuroendocrine and neural profiles of neuroblastomas,ganglioneuroblastomas, and ganglioneuromas. Am J Pathol 1990,136:375-382.12. Aoyama C, Qualman SJ, Regan M, Shimada H: Histopathologic features ofcomposite ganglioneuroblastoma. Immunohistochemical distinction ofthe stromal component is related to prognosis. Cancer 1990, 65:255-264.13. Hsiao CC, Huang CC, Sheen JM, Tai MH, Chen CM, Huang LL, Chuang JH:Differential expression of delta-like gene and protein in neuroblastoma,ganglioneuroblastoma and ganglioneuroma. Mod Pathol 2005,18:656-662.doi:10.1186/1752-1947-5-322Cite this article as: Fatimi et al.: Ganglioneuroblastoma of the posteriormediastinum: a case report. Journal of Medical Case Reports 2011 5:322.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitFatimi et al. Journal of Medical Case Reports 2011, 5:322http://www.jmedicalcasereports.com/content/5/1/322Page 4 of 4

Ganglioneuroblastoma of the posterior mediastinum: a case report.

Abstract
          
            Introduction
            Ganglioneuroblastoma is a rare peripheral neuroblastic tumor that is derived from developing neuronal cells of the sympathetic nervous system, and is found mostly, but not exclusively, in babies and young children.
          
          
            Case presentation
            To the best of our knowledge, there have been no previously reported cases of ganglioneuroblastoma of the mediastinum from Pakistan. We present a case of ganglioneuroblastoma in an eight-year-old Pakistani Sindhi boy incidentally found to have a large posterior mediastinal mass that on biopsy initially looked like ganglioneuroma. He underwent successful excision of the mediastinal mass and remained stable post-operatively. Final pathology findings showed a ganglioneuroblastoma. He has remained free of symptoms on long-term follow-up.
          
          
            Conclusions
            The rarity of this tumor along with its almost exclusive occurrence in the pediatric population necessitates a thorough investigation of patients presenting with a symptomatic mass.
          </jats:sec

Crossref

CASE REPORT Open Access
Ganglioneuroblastoma of the posterior
mediastinum: a case report
Saulat H Fatimi1, Samira A Bawany2 and Awais Ashfaq2*
Abstract
Introduction: Ganglioneuroblastoma is a rare peripheral neuroblastic tumor that is derived from developing
neuronal cells of the sympathetic nervous system, and is found mostly, but not exclusively, in babies and young
children.
Case presentation: To the best of our knowledge, there have been no previously reported cases of
ganglioneuroblastoma of the mediastinum from Pakistan. We present a case of ganglioneuroblastoma in an eight-year-
old Pakistani Sindhi boy incidentally found to have a large posterior mediastinal mass that on biopsy initially looked like
ganglioneuroma. He underwent successful excision of the mediastinal mass and remained stable post-operatively. Final
pathology findings showed a ganglioneuroblastoma. He has remained free of symptoms on long-term follow-up.
Conclusions: The rarity of this tumor along with its almost exclusive occurrence in the pediatric population
necessitates a thorough investigation of patients presenting with a symptomatic mass.
Introduction
Ganglioneuroblastoma is a rare variety of peripheral neuro-
blastic tumor (neuroblastoma) that can arise anywhere
along the sympathetic nervous system. It occurs almost
exclusively in the pediatric population, with some reported
cases in the adult population. It is the third most common
childhood malignancy after leukemia and brain tumors,
and is the commonest solid extracranial tumor among chil-
dren [1]. Its true global incidence, however, is unknown.
According to the Surveillance, Epidemiology and End
Results (SEER) Registry maintained by the National Cancer
Institute, the annual incidence of neuroblastoma is 7.6 per
1,000,000 population in the USA [2]. Of these cases, no
statistics regarding the subtype of ganglioneuroblastoma
are available. Here, we present the case of an eight-year-old
previously healthy boy who presented to our clinic with
non-specific signs and symptoms of pain and was later
diagnosed to have ganglioneuroblastoma.
Case presentation
An eight-year-old otherwise previously healthy Pakistani
Sindhi boy presented to our clinic with complaints of
right-sided lumbar pain for a week. At initial clinical
assessment our patient’s weight was 36.3 kg and his
height was 142 cm. His overall nutritional status was
good and had a normal height and build for his age with
no history of weight loss. He had no other associated
comorbidities. His family history was significant for dia-
betes mellitus, hypertension and untreated pancreatic
cancer and renal cancer. The rest of his history and test
results were unremarkable. A physical examination was
grossly unremarkable. Ultrasound of the abdomen was
performed, with normal results. A chest X-ray was per-
formed that showed a homogenous soft tissue density
mass in the posterior mediastinum with no evidence of
rib erosion. To evaluate the mass further, an MRI was
performed (Figure 1). The dimensions of the mass were
7.3 × 6.0 cm.
A computed tomography (CT)-guided biopsy of the
mass was advised, which was carried out under general
anesthesia. No complications were observed after the
procedure and a post-procedural CT scan did not reveal
any pneumothorax. Histopathology of the biopsy material
showed multiple cones of tissue exhibiting spindle-
shaped cells arranged haphazardly, having moderate
cytoplasm and wavy spindle shaped nuclei. Scattered
mature ganglion cells were also identified, characterized
by abundant cytoplasm and round to oval nuclei; as such
no immature element was identified nor was there any
* Correspondence: ashfaq.awais@gmail.com
2Aga Khan University, Stadium Road, Karachi 74800, Pakistan
Full list of author information is available at the end of the article
Fatimi et al. Journal of Medical Case Reports 2011, 5:322
http://www.jmedicalcasereports.com/content/5/1/322 JOURNAL OF MEDICAL
CASE REPORTS
© 2011 Fatimi et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
evidence of increased mitosis or areas of necrosis. The
specimen was also treated with immunohistochemical
stains and was found to be positive for S-100, synapto-
physin, chromogranin, and leucocyte common antigen
(LCA). These morphological and immunohistochemical
findings were consistent with a diagnosis of ganglioneur-
oma, since no malignant features were identified.
In addition, whole body skeletal scintigraphy was per-
formed with Tc-99 m for metastatic investigation, which
showed bilateral symmetrical tracer distribution in both
the axial and appendicular skeleton with no areas of
abnormal tracer accumulation and normal excretion of
the tracer from both kidneys and urinary bladder.
Bone marrow aspirate and trephine from the iliac crest
performed for staging of the tumor showed all three cell
lines with normal erythroid and myeloid precursors. The
specimen was stained with hematoxylin and eosin and a
few atypical mononuclear cells were noted; however, the
sample was inadequate showing mainly cartilage, muscle
and clot, and was hence non-diagnostic. There was noth-
ing to suggest malignancy or granuloma in the sections
examined. It was suggested to repeat an adequate length
bone marrow trephine if there was a clinical indication to
do so.
Surgery was planned for resection of tumor. Prior to
that, pre-operative evaluation included a normal com-
plete blood count, coagulation profile and serum lactate
dehydrogenase levels. Surgery was approached using left
thoracotomy. After entering the chest cavity, tumor was
excised from the aorta, subclavian vessels and vertebral
column. After adequate hemostasis, chest tubes were
placed and routine closure of thoracotomy was carried
out. The resected mass measuring 9.5 × 7 × 4.5 cm was
sent for histopathology that confirmed the pre-operative
diagnosis and presence of tumor-free margins.
Post-operatively, our patient remained hemodynami-
cally stable. He received intravenous antibiotics and epi-
dural marcaine infusion for pain relief, which was
switched over to oral antibiotics and intravenous analge-
sics. Our patient was running a fever by the third post-
operative day, which was followed by a transient episode
of desaturation; however this improved without conse-
quence. A post-operative chest X-ray was also unre-
markable. On the fourth post-operative day our patient
was discharged from the hospital on oral augmentin and
non-steroidal anti-inflammatory drugs (NSAIDs) for
pain. At discharge, the wound was clean, healing and
healthy.
At follow-up a week later our patient’s condition was
stable. The final post-resection histopathology report
showed a circumscribed and partially capsulated neo-
plasm composed of spindle cells arranged irregularly in
short fascicles, scattered ganglion cells and abundant
cytoplasm. Some nodules within the mass showed small,
round neoplastic cells, scant cytoplasm, increased
nuclear to cytoplasmic ration and hyperchromatic
nuclei. The mitotic rate was identified as two to three
cells per high-power field and the mitosis karyorrhexis
index (MKI) was < 2%. Focal areas of hemorrhage and
necrosis were also identified. Sections of tissues were
also stained with immunohistochemical stains and were
found to be positive for neurofilament, synaptophysin
and chromogranin. The features showed that the tumor
was a ganglioneuroblastoma, nodular type, which are
composite Schwannian stroma-rich/stroma-dominant
and stroma-poor element.
At a year later our patient had complaints of some
bone pain for which a skeletal survey was performed
and was found to be within normal limits. Our patient
has thereafter remained stable.
Figure 1 MRI scan showing homogenous soft tissue density mass in the posterior mediastinum. (a) Sagittal section. (b) Axial section.
Fatimi et al. Journal of Medical Case Reports 2011, 5:322
http://www.jmedicalcasereports.com/content/5/1/322
Page 2 of 4
Discussion
Ganglioneuroblastoma is an uncommon peripheral neuro-
blastic tumor. The International Neuroblastoma Pathology
Classification, popularly known as the Shimada system,
grades these into four distinct categories based upon the
histopathological balance between neural-type cells (primi-
tive neuroblasts, maturing neuroblasts, and ganglion cells)
and Schwann-type cells (Schwannian-blasts and mature
Schwann cells). These include neuroblastomas (Schwan-
nian stroma-poor), ganglioneuroblastoma intermixed
(Schwannian stroma-rich), ganglioneuroma (Schwannian
stroma-dominant) and ganglioneuroblastoma nodular
(composite Schwannian stroma-rich/stroma-dominant
and stroma-poor) and neuroblastic tumors unclassifiable
[3].
Ganglioneuroblastoma have intermediate malignant
potential, between that of neuroblastomas and ganglio-
neuromas. Histologically, they are considered malignant
because they contain primitive neuroblasts along with
mature ganglion cells. In contrast, their benign counter-
parts, ganglioneuromas are fully differentiated tumors
that contain all mature cell types but lack the immature
elements (such as neuroblasts), atypia, mitotic figures,
intermediate cells, or necrosis [4].
Ganglioneuroblastomas occur with equal frequency in
both the genders and most commonly in babies and in
young children, with occurrence after 10 years of age
being extremely rare [4]. They occur most commonly in
the adrenal medulla, extra-adrenal retroperitoneum, and
posterior mediastinum, with the neck and pelvis being less
common sites of occurrence [5]. Thus, the occurrence of a
posterior mediastianal ganglioneuroblastoma in our eight-
year-old patient made this a rarity.
When dealing with pediatric masses, differentials such as
rhabdomyosarcomas, Wilms tumor, germ cell tumors, and
so on, should be taken into consideration. Rhabdomyosar-
coma is the most common soft tissue sarcoma in children
and usually originates in the head and neck (28%), extre-
mities (24%), and genitourinary (GU) tract (18%). The
cause is unclear; however, several genetic syndromes such
as neurofibromatosis, Li-Fraumeni syndrome, and so on,
are associated with it. Symptoms usually depend on the
location and the tumours usually present as an expanding
mass. Wilms tumor, by contrast, is the most common can-
cer of the kidneys in children. The majority are unilateral,
encapsulated, vascularized, and usually do not cross the
midline of the abdomen. They can go undetected early on
because the tumor can grow large without causing pain.
Children usually present with abdominal swelling or blood
in the urine.
Patients with ganglioneuroblastoma often present
clinically with pain caused by either the primary tumor
or by metastatic disease. Patients with mediastinal
tumors can present with stridor and shortness of breath
secondary to tracheal deviation or narrowing. Large
thoracic tumors can cause mechanical obstruction
resulting in superior vena cava syndrome. Nerve or
nerve root compression by the mass can result in per-
ipheral neurological signs. Patients with cervical masses
can present with Horner’s syndrome [6]. However, in
our patient these classical signs and symptoms were not
present and the only complaint was that of non-specific
lumbar pain.
Histological confirmation is required for definitive diag-
nosis. Tissue is obtained by incisional biopsy of the pri-
mary tumor or bone marrow trephine/aspirate in patients
suspected of having metastatic disease in the bone
marrow.
The most common site for metastasis in ganglioneuro-
blastomas is bone, which may mean patients present with
limping and unexplained irritability (Hutchinson’s syn-
drome). Another site of metastasis is the liver. Pepper syn-
drome is the presence of large liver metastases in babies
such that intra-abdominal pressure becomes so high that
there might be possibility of respiratory compromise. In
children younger than a year old, skin metastases are com-
mon, which are darkly pigmented masses resembling blue-
berries (hence it is called ‘blueberry muffin’ syndrome) [7].
In our patient, investigation was performed to rule out
metastasis and was found to be negative.
A CT scan is the imaging modality of choice to evalu-
ate neuroblastic tumors. There is enough evidence to
suggest that it is superior both in terms of determining
tumor size and other characteristics including organ of
origin, tissue invasion, vascular encasement, lymphade-
nopathy, and calcifications [5].
The prognosis for patients with localized disease and
younger age is better; several screening programs were
developed for the detection of neuroblastoma in infancy
by measuring urinary catecholamines [8] but were not
associated with any difference in mortality. As a result,
they are not routinely recommended.
Age is taken into account when defining neuroblas-
toma histology as favorable or unfavorable. The younger
the age at diagnosis, the better the survival rate [8] with
children younger than a year old having considerably
better survival than older children. Even the outcome of
favorable or less aggressive neuroblastomas is worse in
older children [9]. Hence, although it is not rare in the
literature to find reports of good outcomes, the excellent
results and successful follow-up in our patient is of sig-
nificant note.
Mediastinal neuroblastomas are better in terms of
prognosis than abdominal neuroblastomas in that
patients with the former tend to present earlier when
the size is still small, and hence complete resection of
Fatimi et al. Journal of Medical Case Reports 2011, 5:322
http://www.jmedicalcasereports.com/content/5/1/322
Page 3 of 4
the tumor is possible [10]. Complete excision remains
the mainstay of therapy of localized mediastinal neuro-
blastomas. There are no reports of the recommended
duration of follow-up; however, follow-up is required
with chest X-ray. The two-year event-free survival rates
are 85% to 100%; relapses can be salvaged by further
surgery or chemotherapy [11].
Differential markers for distinguishing ganglioneuro-
mas from ganglioneuroblastomas at present are not
available; immunohistochemical stains with antibodies
such as neurofilament, synaptophysin, chromogranin,
s-100 and LCA are generally positive in both ganglio-
neuromas and ganglioneuroblastomas [12]. However it
has been shown on post-mortem histopathology speci-
mens that an epidermal-growth-factor-like protein called
delta-like (dlk), which regulates the differentiation of
neuroblastoma cell lines, showed stronger expression in
the ganglioneuroma cell lines and weaker expression in
ganglioneuroblastoma cell lines [13], probably suggesting
the loss of this differentiation factor in the progress
toward the malignant disease.
Conclusions
The rarity of ganglioneuroblastoma, along with its
occurrence in the pediatric population, warrants a great
deal of suspicion when a younger patient presents with
a symptomatic mass. Given the wide variety of clinical
symptoms the tumor can present with, it is essential
that neuroblastoma remains as one of the differential
diagnoses while working on such a case.
Consent
Written informed consent was obtained from the
patient’s next-of-kin for publication of this case report
and any accompanying images. A copy of the written
consent is available for review by the Editor-in-Chief of
this journal.
Author details
1Section of Cardiothoracic Surgery, Department of Surgery, Aga Khan
University, Stadium Road, Karachi 74800, Pakistan. 2Aga Khan University,
Stadium Road, Karachi 74800, Pakistan.
Authors’ contributions
SHF analyzed our patient’s details and was primarily responsible for
obtaining the full investigation results, including the surgery performed on
our patient. SAB was involved in assisting the primary faculty, obtaining
relevant details about the case and confirming its rarity, and was a major
contributor to writing the manuscript. AA contributed a significant effort to
writing the manuscript and editing the final draft. All authors read and
approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 20 July 2010 Accepted: 22 July 2011 Published: 22 July 2011
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doi:10.1186/1752-1947-5-322
Cite this article as: Fatimi et al.: Ganglioneuroblastoma of the posterior
mediastinum: a case report. Journal of Medical Case Reports 2011 5:322.
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(Eds): SEER Cancer Statistics Review,

Carlson CL: Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic-pathologic correlation. Radiographics

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Djokić D: The characteristics of mediastinal neuroblastoma and perspectives on surgical excision. Acta ChirIugosl

DM: Infantile neuroblastoma presenting with cutaneous blanching nodules.

Histopathologic features of composite ganglioneuroblastoma. Immunohistochemical distinction of the stromal component is related to prognosis. Cancer

JM: Neurogenic tumors in the abdomen: tumor types and imaging characteristics. Radiographics

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http://doaj.org/search?source=%7B%22query%22%3A%7B%22bool%22%3A%7B%22must%22%3A%5B%7B%22term%22%3A%7B%22id%22%3A%22b544659c09b7495980f782d0cac4e209%22%7D%7D%5D%7D%7D%7D

Ganglioneuroblastoma of the posterior mediastinum: a case report.

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