Bilateral hemorrhagic cystic adrenal neuroblastoma with liver and lymph nodal metastases in an infant.

A 6-month-old boy presented with pallor, large left hypochondrial mass and hepatomegaly. Computerized tomography (CT) revealed cystic lesions in bilateral adrenals, liver and retroperitoneal lymph nodes and a lytic left femur lesion. There was hemorrhagic aspirate with round blue cells. Excised left sided mass with adjacent lymph nodes and biopsies of others confirmed well differentiated neuroblastoma. He received 4 cycles of chemotherapy with remaining lesions markedly reduced at 2 months CT scan. At 2 year follow up he is doing well.

INTRODUCTION

Bilateral cystic adrenal neuroblastoma with cystic liver and lymph nodal metastases and generalized intratumoral hemorrhage is extremely rare.[12] An infant with this rare presentation managed successfully is presented.

CASE REPORT

A 6-month-old boy presented with abdominal discomfort of 15 days duration and a mass noticed for the past 2 days. There was history of constipation off and on for the past 3 months. He was born at term by Caesarean section for fetal bradycardia and had a normal antenatal ultrasonography.

On examination, he was active, alert, weighed 6.1 kg, blood pressure 100/60 mm Hg and pulse rate 90/min. He had low set ears with brachycephaly. He was pale with no cyanosis or icterus. The skin was normal. An irregular, firm, 6 × 8 cm size mass was palpable in the left hypochondrium. A non tender liver was palpable 2 finger breadths below the costal margin with a prominent right lobe. His hemoglobin was 7g/ dL, total leukocyte count 15,040/mm3 and platelet count 454×103/ mm3. The electrolytes, renal and liver function tests were within normal limits except SGOT [82.5 U/L (range 15-60)]. The chest radiograph showed opacification in the perihilar region. An ultrasonography (USG) of the abdomen showed bilateral adrenal space occupying lesions suggestive of hemorrhage. USG guided fine needle aspiration cytology (FNAC) of the left sided mass withdrew hemorrhagic fluid with few clusters of round blue cells with scanty cytoplasm. A whole body bone scan showed increased osteoblastic activity in the left upper end of femur. A contrast enhanced computed tomographic (CECT) scan of the abdomen [Figure 1] showed a 9.1×8.5×5.6 cm hypodense predominantly cystic mass in the left adrenal gland area with multiple linear calcifications and a similar lesion 2.2×1.4 × 1.4 cm in size in the right adrenal gland. There were multiple hypodense lesions in the liver and a few prominent upper retroperitoneal nodes with central necrosis and calcification. There was a small lytic lesion with cortical breach in the shaft of left upper femur. The spleen was normal. His N-myc was in range (1%) and no gene amplification was detected on assay. There was no bone marrow involvement on bilateral trephine biopsy.

Figure 1

CECT abdomen shows a large cystic mass in the left adrenal region pushing the kidney inferiorly and cystic lesions in the right adrenal area and liver

At laparotomy, a 10×9 cm cystic lesion arising from the left adrenal gland pushing down the kidney and adherent to the splenic capsule and adjacent mesocolon and a prominent draining vessel was excised without spillage. A large lymph nodal mass with variegated consistency engulfing the renal vessels and extending into the preaortic area was excised. The right adrenal gland had a variable consistency with multiple cysts, 1-2 cm in size. They yielded a bloody aspirate, cytology being similar to the left side. The liver surface showed multiple 5 mm size hemorrhagic cysts, more so in the right lobe and one of them was biopsied. The histopathology of the left adrenal mass showed overall features of a differentiating neuroblastoma [Figure 2]. The sections from lymph nodes and liver showed metastasis with hemorrhagic necrosis.

Figure 2

Histopathology of left adrenal mass showing (a) Clusters of tumors cells amidst areas of calcification and fibrinous exudates (H and E, ×40). (b) Neoplastic cells present in diffuse sheets interspersed by fine fibrovascular septa (H and E, ×200). (c) Higher magnification showing small, round to oval cells with high N/C ratio, and stippled chromatin. Few Homer-Wright rosettes are also seen (H and E, ×400). (d) Neoplastic cells positive with neuron-specific enolase (NSE), (immunoperoxidase, ×400)

The child had an uneventful postoperative recovery. He received 4 cycles of etoposide (12.5 mg/kg) and carboplatin (6.6 mg/kg) at 3 week intervals. A CECT done after 2 cycles of chemotherapy showed few focal hypodense lesions in segment VI of liver and multiple small lymph nodes in retroperitoneum, left suprarenal, aortocaval and paraaortic location. Serial USGs since then have shown complete resolution of these lesions. At 2 year follow up he is asymptomatic and thriving well.

DISCUSSION

Adrenal neuroblastoma is a common solid malignant childhood tumor with bilateral presentation occurring in only 10% cases.[3] Bilateral cystic adrenal neuroblastomas are very rare. Differential diagnosis includes adrenal hemorrhage, abscess, adrenal cytomegaly, dilated upper pole renal calyces etc.[24] Bilateral hemorrhagic adrenal cysts resolving spontaneously have been reported in an incomplete form of Beckwith-Weidemann syndrome.[5] However, the presence of hepatic cystic lesions and multiple linear calcifications in the mass pointed to a neuroblastoma. Our patient presented with anemia, secondary to intracystic hemorrhage. This can be life threatening.[167] The platelet counts were normal ruling out consumptive coagulopathy.

Unlike Wilms’ tumor, associated congenital anomalies are rare with neuroblastoma. However, Miller et al. showed an increased incidence of brain and skull defects in 2% children with neuroblastoma.[8] Our patient had low set ears and brachycephaly and interestingly there was a previous pregnancy that had been aborted following a diagnosis of Arnold Chiari malformation pointing to a genetic influence in the etiology. Histopathological differentiation from other tumors was possible in our case as the tumor was positive for neuron specific enolase. The tumor also showed penetration of the pseudocapsule and infiltration of surrounding tissue which is often seen with neuroblastoma.

Metastatic spread in neuroblastoma most commonly occurs to the liver.[1279] In addition, our patient also had a lytic bone lesion. Interestingly, there was a great difference in size between the tumors on either side as observed in previous reports also, giving rise to a speculation that the left sided tumor was the primary and the other a metastatic lesion.[12]

Although cystic neuroblastomas have a good prognosis and may regress spontaneously, early excision is advisable. Bilaterality, large left sided lesion, generalized tumoral hemorrhage and bone cortex metastasis in an infant prompted us to excise the larger mass with aspiration of the smaller adrenal mass followed by chemotherapy. The case is reported because of its rarity and good response to treatment.