Adolescent Neuroblastoma of Lower Limb.
Rajeshwari K, Assistant Lecturer, Department of Pathology,
Nandkumar V Dravid, Professor and Head, Department of Pathology,
Nandkishor Goyal, Associate Professor, Department of Orthopaedics,
Arundhati Gadre, Assistant Lecturer, Department of Pathology,
Smita Pawar, Assistant Lecturer, Department of Pathology,
ACPM Medical College Dhule Maharashtra,
Karibasappa GN, Associate Professor, Department of Community Dentistry,
ACPM Dental College Dhule, Maharashtra.
Address for Correspondence
Dr. Rajeshwari K,
#8 Staff quarters,
A.C.P.M Medical College,
Sakri Road, Dhule,
Rajeshwari K, Dravid NV, Goyal N, Gadre A, Pawar S, Karibasappa GN. Adolescent Neuroblastoma of Lower Limb. Online J Health Allied Scs.
2013;12(1):9. Available at URL:
Open Access Archives
Submitted: Feb 8,
2013; Accepted: Mar 29, 2013; Published: Apr 15, 2013
Neuroblastoma is the third most common extracranial solid tumor in
childhood next to lymphomas and brain tumours. It originates from the neural crest. The mean age of diagnosis
is 2 years, with 35% of the cases occurring before the age of 1 year and the remaining occurring before
10 years of age.(1) Very rarely less than 5% of patients are diagnosed during adolescent age group.(2) The
most common site of involvement of neuroblastoma is the abdomen (60%), followed by the thorax (15%), pelvis
(5%) and the cervical sympathetic chain (5%)(3) and very rarely in the lower limb first reported by Mackay in
1976.(4) Neuroblastoma in the lower limb account for <1% of all soft tissue neoplasms.(5)
Here we report a case of neuroblastoma of lower limb in an adolescent age group which is uncommon for
its site and age in the patient which clinically and radiologically mimicked chronic osteomyelitis.
Later the diagnosis of neuroblastoma of lower limb was made with the help of fine needle aspiration cytology,
histomorphology and immunohistochemistry.
A 16 years old male patient presented to an Orthopaedician with history of large soft tissue
swelling, pain and foul smelling discharging sinuses of right lower leg since 4 months. Patient had history of
anorexia and weight loss of about 10 kgs since 6 months. Past history of similar complaints of swelling, pain and foul smelling discharging sinuses was present 6 months back
where the clinical and radiological findings mimicking chronic osteomylitis. On general examination pallor was
present. Systemic examination were within normal limits. Local examination revealed 15x11cm swelling,
firm to hard circumscribing the posterior aspect of midshaft of tibia having pathological fracture, with
multiple reddish foul smelling discharging sinuses on to the scarred skin. Routine haematological
investigation showed low haemoglobin, leucocytosis with raised erythrocyte sedimentation rate.
Biochemical parameters were within normal limits. Radiology of right lower leg anteroposterior and lateral view showed
progressive destruction with pathological fracture of tibia with large mass in the calf not attached to
bone and fibula showed sclerosis, osteolysis and bowing.(Figure 1) USG abdomen revealed paraarotic
lymphadenopathy with multiple hyperechoic masses in between the normal hepatic parenchyma suggestive of
secondaries in the liver. Fine Needle Aspiration Cytology (FNAC) of right lower leg swelling was positive for malignant cells suggestive
of malignant small round cell tumour. In view of malignant neoplasm, pathological fracture, chronic
discharging sinuses of right leg patient underwent right knee disarticulation and the specimen was sent
for pathological examination.
Gross findings: Disarticulated right knee measured 35 cms in length with the tumour mass measured 13x10cm, firm to hard, encompassing the fracture area of tibia and fibula displacing calf muscles not attached to bone (Figure 2) with multiple discharging sinuses on to the scarred skin. The tumour mass
on cut section showed fleshy appearance with large lobulated grayish white tumour mass with areas of
haemorrhage and necrosis.
Figure 1: Radiology of right leg AP and Lateral view showing progressive destruction with pathological fracture of tibia with large mass in the calf not attached to bone and fibula showing sclerosis, osteolysis and bowing.
Figure 2: The tumour mass encompassing the fracture area of tibia and fibula displacing the calf muscles.
Histopathology: Serial sections of the tumour mass showed tumour cells arranged in lobules, sheets and islands of small round tightly packed cells. Tumour cells were uniform, round in shape with round to oval nuclei having granular chromatin with indistinct cytoplasm. The islands of tumour cells were separated from each other by variable background, fibrovascular stroma and abundant eosinophilic neurofibrillary material of neuroblastoma which is a striking feature. Tumour cells were arranged in rosettes suggesting features of Flexner as well as Homer-Wright rosettes with extensive tumour tissue infiltrating into the surrounding tissues (Figures 3 and 4). Special stain like Periodic Acid Schiff was negative. Histopathological diagnosis of poorly differentiated neuroblastoma of lower limb was made. Immunohistochemical analysis revealed focal positivity for synaptophysin and Chromogranin and CD 99 was negative. (Figures 5A, 5B and 5C respectively) which confirmed the diagnosis of neuroblastoma. In view of involvement of lymph nodes, liver, skin, patient was grouped under the stage 4 neuroblastoma and was immediately put on chemotherapy and radiotherapy. In follow up patient developed bilateral inguinal lymphadenopathy with chest pain and breathlessness. FNAC of inguinal lymphnode and chest x-ray showed metastatic tumour deposits in lymph node and lung parenchyma respectively. Six weeks later patient expired.
Figure 3: Skin with underlying tumour mass with lobular and sheet like pattern.(hematoxylin and eosin stain, ×100)
Figure 4: Tumour cells are uniform, round with round to oval nuclei having granular chromatin with Flexner and Homer-Wright rosettes (hematoxylin and eosin stain, ×400)
Figure 5A -Synaptophysin focal Positivity
Figure 5B: Chromogranin focal Positivity
||Figure 5C: CD 99 Negative
Neuroblastomas in adolescent account for <5% (2) and around <1% of all soft tissue sarcoma of lower limb.(5) Neuroblastoma involves 3 classical histopathological types by differentiation and maturation. These include the neuroblastoma, ganglioneuroblastoma and ganglioneuroma tumors. In most cases of neuroblastomas, have a nonestablished etiology, sometimes environmental factors also appear to be involved. The diagnosis of neuroblastoma in adolescent and adult is very difficult as it includes various differential diagnosis like Rabdomyosarcoma, Ewing’s sarcoma, Non Hodgkin’s Lymphoma, Small cell carcinoma, Nephroblastoma. The most diagnostic feature on light microscopy of neuroblastoma is the presence of rosettes, background showing eosinophilic neurofibrillary material and ganglion cell differentiation. The definitive diagnose of neuroblastoma by fine needle aspiration cytology alone is very difficult unless there are Homer-Wright rosettes and neurofibrillary material. Hence combined cytological and histomorphological features are considered in the diagnosis of either the primary or metastatic neuroblastoma. Only one reference has been found relating to FNAC diagnosis in an adult.(6) Compared to children, neuroblastomas occurring in adults and adolescents usually present early in advanced stage and with metastasis (7), as seen in our case report.
Neuroblastomas can metastasize widely through both lymphatic and vascular routes. The most common sites
of metastasis are bone marrow, bones, lymph nodes, liver, skin, and testes. There is a greater frequency of unusual
metastases among adolescents in parenchyma of the lung or brain.(8)
The treatment of neuroblastoma is surgery, chemotherapy (include alkylating agents like cyclophosphamide/ifosfamide, platinum-based agents like cisplatin/carboplatin, etoposide, adriamycin and vinca-alkaloids) or radiotherapy, stem cell transplantation, immunotherapy (monoclonal antibodies - anti –GD2), radioisotope iodine 131- MIBG and NYMC amplification.(9) The prognosis of the patients with neuroblastoma depends on numerous variables; the most important of them are age of the patient at diagnosis and the stage of the tumor, DNA ploidy, histology, and chromosome 1p, 11q, 17g aberration.(10) Two important favourable prognostic features of neuroblastoma are the age and the stage of the tumour at the time of diagnosis.
Our case report illustrates neuroblastoma as an extremely rare neoplasm in adolescents with rare site of lower limb presentation. Neuroblastoma diagnosed in adolescents has got poor prognosis as it presents with advanced stage at the time of the presentation. Neuroblastoma in the lower limb is often misdiagnosed as chronic osteomyelitis, but the actual nature of the disease becomes apparent after a considerable period of time. Hence, combined investigations like radiodiagnosis, ultrasound, fine needle aspiration, histomorphology and immunohistochemistry are useful in the accurate diagnosis of neuroblastoma. Hence one should include neuroblastoma as one of the differential diagnosis of small round cell tumours even at rare site and age of presentation. As there are newer modalities of early diagnostic tests and well advanced treatments that increase the survival rate of the patient, high index of suspicion is needed in early diagnosis and prompt intervention to improve prognosis and reduce the morbidity.
- McLean TW, Iskandar SS, Shimada H, Hall MC. Neuroblastoma in an adult. Urology. 2004;64:1232.
- Rubie H, Hartmann O, Michon J, et al. N-Myc gene amplification is a major prognostic factor in localized neuroblastoma: results of the French NBL 90 study. Neuroblastoma Study Group of the Societe Francaise d’Oncologie Pediatrique. J Clin Oncol. 1997;15:1171–1182.
- Armstrong EA, Harwood-Nash DC, Ritz CR, et al. CT of neuroblastomas and ganglioneuromas in children. AJR. 1982;139:571–576.
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- Feldman PS, Covell JL, Silverman JF et al. The diagnosis of neuroblastoma by fine needle aspiration cytology(Abstract). Acta Cytol 1985;29:950.
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- Navid F, Armstrong M, Barfield RC. Immune therapies for neuroblastoma. Cancer Biol Ther. 2009;8:874–882.
- Esiashvili N, Goodman M, Ward K, Marcus RB Jr, Johnstone PA. Neuroblastoma in adults: incidence and survival analysis based on SEER data. Pediatr Blood Cancer. 2007;49:41-46.