Primary congenital sacrococcygeal neuroblastoma: A case report with immunohistochemical study and review of literature.

Primary localized congenital sacrococcygeal neuroblastomas (SCNs) are rare. Diagnosis is based on histological and immunohistochemical evaluation, which is indispensable not only for determining tumor type but also for predicting biological behavior. We report a rare case of congenital SCN in a 9-month-old baby girl. Based on clinical and radiological findings, a provisional diagnosis of solid variant of sacrococcygeal teratoma (SCT) was made. The swelling was entirely excised. On histopathological examination, diagnosis of neuroblastoma, differentiating type in the sacrococcygeal region was considered. On immunohistochemistry, the tumor cells showed immunoreactivity for markers such as neuronspecific enolase, chromogranin-A, synaptophysin, and cyclin D1. S-100 showed positive cytoplasmic immunoreactivity. CD99, leucocyte common antigen, PanCK, and epidermal growth factor receptor were nonreactive. Cyclin D1 showed strong nuclear immunoreactivity. p53 was negative and Ki67 labelling index was less than 1%. The immunohistochemical markers studied, confirmed the histopathological diagnosis, and the cell proliferative index markers indicated it to be a very low grade lesion. Postoperatively, the child is disease-free and has achieved normal milestones for age for period of 6 months.

Introduction

Neonatal tumors represent 2% of childhood malignancies of which teratoma and neuroblastoma are the common types.[1] Neuroblastoma is the commonest extracerebral solid tumor of childhood.[2] It is an embryonal tumor of the autonomic nervous system arising from neural crest tissue.[3] About 70% of the neuroblastomas occur in the retroperitoneum and majority of these involve the adrenal gland.[4] The other sites mentioned are intrathoracic, neck, and pelvis. Pelvic neuroblastoma is a rare location, the incidence being 3.4%.[5] Malignant lesions presenting in the sacrococcygeal region are most often SCT.[6] We encountered a case of primary congenital SCN in a 9-month-old baby girl which was surgically excised. The immunohistochemical markers studied, confirmed the histopathological diagnosis, and the cell proliferative index markers indicated it to be a very low grade lesion, which has prompted us to report this case along with review of literature.

Case Report

Clinical history

A 9-month-old baby girl brought to pediatric surgery outpatient department, presented with swelling in the sacral region since birth. The swelling was initially small and later increased to present size. Local examination showed round and globular swelling measuring 6 × 5 cm. Overlying skin was unremarkable. Systemic examination findings were noncontributory. The female child was born full term by uneventful normal vaginal delivery. She achieved normal milestones for age and was immunized appropriately for age. Laboratory investigations such as liver function tests, renal function tests, plasma glucose levels, and chest X-ray were normal.

Magnetic resonance imaging findings of the sacrococcygeal mass: T2W sagittal images showed a well-defined lobulated lesion in the pre and retro sacrococcygeal region, encasing the coccyx. The lesion was isointense to hyperintense in signal intensity and showed fine internal septations within [Figure 1]. On the basis of clinical and radiological findings, a provisional diagnosis of solid variant of sacrococcygeal teratoma (SCT) was made.

Figure 1

Magnetic resonance imaging findings of the sacrococcygeal mass: T2W sagittal images showed a well-defined lobulated lesion in the pre- and retro sacrococcygeal region, encasing the coccyx. The lesion was isointense to hyperintense in signal intensity and showed fine internal septations within

Caudal and general anesthesia was given and the swelling was entirely excised with the part of the coccyx. Postoperative course was uneventful.

Pathological examination

On gross examination, the tumor was well-circumscribed having smooth and lobulated external surface, firm in consistency, and measured 6 × 6× 5 cm. On cut section, the tumor appeared nodular, greyish white with focal hemorrhagic areas in the periphery [Figure 2].

Figure 2

Macroscopic features of tumor (external and cut surface)-External surface shows a partially capsulated (capsule thickness varying from area to area), firm brown tumor having a bosselated surface measuring 6 × 6 × 5 cm. On cut section, the tumor appeared nodular, greyish white with tiny foci of hemorrhages at the periphery

On microscopic examination, a well-circumscribed tumor composed of round to oval cells with prominent nucleoli and scanty to moderate cytoplasm. The cells were seen arranged predominantly in nests. Also seen were few sheets and lobules, separated by thick and thin fibrovascular septae. Many areas showed presence of Homer Wright pseudorosettes [Figure 3]. At few places, the tumor showed neuropil and schwannian stroma. Amid this, were noted large cells differentiating into ganglion cells [Figure 3 inset]. There was paucity of abnormal mitotic figures and karyorrhectic activity. On the basis of these findings, diagnosis of neuroblastoma in the sacrococcygeal region was considered and representative sections were subjected to immunohistochemical studies.

Figure 3

Microscopic details of tumor-Areas showing small round cell tumor with Homer Wright pseudorossettes (H and E, ×400). Inset showing neuropil and ganglion cells (H and E, ×1000)

Immunohistochemical findings

Immunohistochemistry (IHC) was performed with the following panel of antibodies utilized for differential diagnosis of small round cell childhood tumors which included neuroendocrine markers like neuronspecific enolase (NSE) (Dako) chromogranin-A (clone 5H7, Leica) and synaptophysin (clone 27G12, Leica). Other markers included were S-100 (Leica), CD99 (clone 12E7, Dako), leucocyte common antigen (LCA) (clone, 2B11 + PD 7126), pancytokeratin (PanCK) (clone AE1/AE3, Dako), epidermal growth factor receptor (EGFR) (clone EGFR.25, Leica), cyclin D1 (clone P2D11F11, Leica), P53 (cloneDO-7, dako) and Ki-67 (clone MIB-1, Dako). Strong cytoplasmic immunoreactivity was observed with NSE [Figure 4a], synaptophysin and it was patchy with chromogranin [Figure 4b]. S-100 showed positive cytoplasmic immunoreactivity. CD99 [Figure 4c], LCA, PanCK, and EGFR were nonreactive. Cyclin D1 showed strong nuclear immunoreactivity [Figure 4d]. P53 was negative and Ki67 labelling index was less than 1%.

Figure 4

Immunohistochemical findings: (a) Tumor cells showing strong cytoplasmic immunoreactivity for neuronspecific enolase (×400), (b) patchy for chromogranin (×400), (c) Tumor cells are non-immunoreactive for CD99 (×400), and (d) shows increased expression for cyclin D1 (×400)

The above histomorphological studies confirmed the diagnosis of low grade primary sacrococcygeal neuroblastoma (SCN).

Discussion

The neuroblastoma was first described by Virchow in 1864. This term was coined by James Hommer Wright in 1910, who first stated that this tumor arises from the incompletely committed precursor cells derived from the neural crest ectodermal tissue.[7] Neuroblastoma can arise at many anatomic sites harbouring sympathetic tissue and commonly arises from adrenal glands.[8] The other peripheral sites are the neck, thorax, and pelvis. These extraadrenal neuroblastomas generally tend to have better prognosis due to their well-differentiated nature.[238] The pelvic neuroblastomas are rare, the incidence being 5% and constitute 0.25% of all neonatal neoplasms.[9] Among the pelvic neuroblastomas, precoccygeal tumors as encountered in the present case, have not been documented to the best of our knowledge.

Few cases of SCNs are reported in literature. Tanaka et al.,[9] mentioned first case of neonatal neuroblastoma mimicking Altman type III SCT in 2005. Similar case of a 2-month-old baby girl with large presacral neuroblastoma was reported subsequently.[9] It is worth noting that the present case clinically and radiologically was thought to be solid variant of teratoma. Rarity of SCN was highlighted by Sebire et al.,[6] who reported one case of SCN among 85 cases of sacrococcygeal neoplastic lesions with an incidence of 1.2%.

As may be expected with disease of developing tissue, neuroblastoma occurs in very young children. The median age at diagnosis is 17 months.[3] Our patient had swelling since birth, gradually increasing, and was operated at 9 months of age. Malignant lesions presenting in the sacrococcygeal region are most often SCT and three-quarters of them are evident at birth.[10]

In literature, one of the large series of localized pelvic neuroblastomas has reported high incidence of neurological symptoms at diagnosis.[9] Our patient was symptom free except for the swelling in the sacrococcygeal region.

At times, the tumor may be dumbbell shaped and deemed unresectable.[9] However in our case, the tumor was kidney-shaped and was excised completely.

The clinical differential diagnosis to be considered in lesions over sacrococcygeal region includes various benign and malignant lesions. Benign lesions include lipoma, hemangioma, meningocele, lymphangioma, pilonidal sinus, dermoid, myxopapillary ependymoma, and epidermoid cysts.[10] Malignant lesions presenting in the sacrococcygeal region are most often SCT especially those presenting at birth.[6] Isolated cases of other malignant lesions in the sacrococcygeal region in this age group have been published, including teratoid Wilms’ tumor, malignant Triton tumor, ependymoblastoma, neuroblastoma.[10]

Histopathological differential diagnosis includes tumors such as Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET), lymphoma, and desmoplastic round cell tumor.[11] Immunohistochemical profile helps in establishing diagnosis. Neuroblastomas are NSE, chromogranin, and synaptophysin positive. ES/PNET occurs in children usually above 5 years of age and is always CD99 and chromogranin-positive. Neuroblastoma occurs in younger age group and is always CD99 negative. LCA is expressed in lymphoma and strong cytokeratin positivity is seen in desmoplastic small round cell tumor in contrast to neuroblastoma.[11]

Cell proliferative markers such as P53 and Ki 67 are of prognostic significance.[11] In the present case P53 was negative and Ki67 showed less than 1% labeling index. EGFR expression was observed in two tissues by IHC and 8 of 10 cell lines by Western blotting.[12] It is worth noting that our case showed no EGFR expression on IHC. Genomic aberrations of cyclin D1 in neuroblastoma indicating dysregulation of the G (1) entry checkpoint is an important cell cycle aberration in this pediatric tumor. Immunohistochemical analysis done by them showed overexpression of cyclin D1 in neuroblasts. They conclude that neuroblastoma functionally depends on overexpression of G (1)-regulating genes to maintain their undifferentiated phenotype.[13] Our case also showed similar overexpression.

SCN though has low mortality, has high morbidity owing to tumor bulk pressure, and probable postoperative neurologic deficit.[9] Patient's age is considered to the best prognostic factor while other factors such as tumor site, stage, histopathology, IHC, tumor lymphoid cell infiltration, urinary catecholamine secretion, serum NSE and ferritin, deoxyribonucleic acid ploidy and N-mync amplification are also considered significant.[14] In our case, the child was less than 1 year, tumor was completely resectable and microscopically differentiated type,[15] with favorable IHC prognostic markers. Hence, case was considered to have favorable prognosis and thus was informed to the parents and the child was discharged. On 6 months follow-up, the child is disease free and has achieved milestones for age.

Our experience with present case highlights the significance of detailed immunohistochemical analysis in each and every case of childhood neuroblastomas. It is hoped that more case studies will elucidate the point further.